Download Regulation of ISWI -family of chromatin remodelling complexes

Regulation of ISWI-family of chromatin remodelling complexes
Maria Toto*, Giulia D’Angelo*, Davide FV Corona
Maria Toto, Giulia D’Angelo, Davide FV Corona
Dulbecco Telethon Institute c/o University of Palermo
Dpt STEBICEF-Viale delle Scienze - Edificio 16
90128-Palermo-Italy
E-mail of the corresponding author: [email protected]
Tel: +39 091 238 97345; Fax: +39 091 238 60721
*These authors contributed equally to this review
Keywords (4 to 6): ISWI, nucleosome, chromatin remodelling, histone
Abstract (150 to 250 words)
The packaging of DNA into chromatin facilitates the storage of the genetic information within the
nucleus but prevents the access to the underlying sequences. The evolutionarily conserved ISWI
family of ATP-dependent chromatin remodelling complexes provide one of the regulatory
mechanisms that eukaryotic cells have evolved to induce structural changes to chromatin. All ISWIcontaining complexes use the energy derived from ATP hydrolysis in order to rearrange
nucleosomes on chromatin to carry specific nuclear reactions. The combination of associated
proteins with the ATPase subunit as well as specific histone modifications specialize the nuclear
function of each ISWI-containing complex. Here we review the many way through which ISWI
enzymatic activity can be modulated and regulated in the nucleus of eukaryotic cells.
Introduction
Eukaryotic cells store their genetic information in the form of chromatin, a complex of DNA packed
with structural and regulatory proteins. The functional repeating unit of chromatin is the nucleosome,
146 base pairs of DNA wrapped around an octamer of histone proteins. While this packaging
provides the cell with the obvious benefit of organizing a large and complex genome in the nucleus, it
can also block access to DNA. Nuclear reactions therefore depend on factors that modulate the
accessibility of DNA within the context of chromatin. ATP-dependent chromatin remodeling and the
covalent modification of histone amino termini, play central roles in determining chromatin
accessibility [ref]. These reactions are catalyzed by evolutionarily conserved multi-subunit chromatinremodeling complexes that directly alter chromatin structure to regulate gene expression and other
nuclear functions [ ref].
ISWI is a component of several ATP-dependent chromatin remodeling complexes conserved in
composition and function across species [ ref] (FIG). In higher eukaryotes, ISWI is an abundant and
ubiquitously expressed protein that is essential for cell viability [ ref]. ISWI chromatin remodellers
are involved in important nuclear functions such as DNA replication, DNA repair, transcriptional
regulation and chromosome structure maintenance [ref]. In order to modulate these essential
biological processes, ISWI activity needs to be finely regulated. To date, work conducted in several
model system has revealed a multitude of ways by which ISWI-chromatin remodelling activity can be
regulated in the nucleus.
Due to the broad spectrum of functions played by ISWI, several nucelar factors influence its function
in order to integrate ISWI activity in different physiological contexts in vivo. Indeed, nucleosome
spacing reactions catalyzed by ISWI can be regulated (1) in cis by intrinsic domains of ISWI protein,
(2) by its associated subunits and other chromatin factors, (3) by post-translational modification of
ISWI itself and of its associated nucleosomal substrate, (4) and finally by specific DNA and RNA
sequence features. Here we present a review of the different mechanisms by which t ISWI enzymatic
activity could be regulated in the nucleus of eukaryotic cells.
(1) Allosteric regulation through structural and functional ISWI domains (add Fig)
Regulation of ISWI chromatin remodelers targeting and activity on nucleosome substrates is
essential to gain knowledge on chromatin dynamics. Since their discovery, different levels of
regulation of ISWI chromatin remodelling activity emerged (Erdel, Krug et al. 2011). Although the
auxiliary subunits of ISWI complexes greatly contribute to the regulation of its activity, recent work
has shed light into the function of its intrinsic domains. Interestingly, studies conducted in
Drosophila and in yeast, demonstrated that the conserved ATPase domain has autonomous
nucleosome remodelling activity while the ATPase adjacent domains have a regulatory function
(Clapier and Cairns 2012; Hota, Bhardwaj et al. 2013; Mueller-Planitz, Klinker et al. 2013).
ISWI contains a highly conserved ATPase core domain located in the N-terminal half of the protein
and a characteristic set of domains, HAND-SANT-SLIDE (HSS), at the C-terminal with DNAbinding function (Grune, Brzeski et al. 2003; Boyer, Latek et al. 2004; Hota and Bartholomew
2011). Over the past few years, in vivo and in vitro studies have led to a broadly accepted model in
which the HSS domain plays an integral part during the remodelling reaction (Boyer, Langer et al.
2002; Grune, Brzeski et al. 2003; Boyer, Latek et al. 2004). Unexpectedly, a recent study showed
that most of fundamental regulatory aspects of nucleosome remodelling are contained within the
compact ATPase module of Drosophila ISWI. In this work the authors found that ISWI lacking its
HSS domain can still remodel nucleosomes, with an intrinsic ability to bind nucleosomes and
functionally interact with H4 N-terminus, revealing a positive role for the HSS domain in increasing
the affinity and specificity of ISWI ATPase for nucleosome (Mueller-Planitz, Klinker et al. 2013).
Similarly, another study showed a regulatory function for the SLIDE domain of Saccharomyces
cerevisiae Isw2 subunit, to help maintaining the directionality of movement of DNA into
nucleosomes (Hota, Bhardwaj et al. 2013). All together these data underline that the accessory
domains of the ATPase core of ISWI may have evolved to optimize catalysis and modulate the
outcome of the reaction. This idea was also supported by the identification of two new conserved
and separate negative regulatory regions of the dISWI ATPase, defined as AutoN and NegC. The
first is located within the N-terminus of ISWI ATPase and has a conserved sequence that resembles
the basic patch of the H4 tail. NegC is located between the ATPase core and the HSS DNA-binding
domain (Fig ?). AutoN inhibits the ATP-hydrolysis rate working as a brake that constrains the
catalytic activity of ISWI by making contact with the ATPase lobes. NegC inhibits ATPase
coupling to DNA translocation. Moreover, mutation of AutoN and NegC enables marked
nucleosome sliding without the H4 basic patch, DNA linker, or the HSS domain, confirming that
the ISWI ATPase core is an intrinsically active DNA translocase, flanked by specific regulatory
modules that ensure remodelling only in the presence of proper nucleosomal epitopes (Clapier and
Cairns 2013).
An integrated view of these and other structural data obtained so far, imply that remodelernucleosome interactions stabilize a conformation of ISWI that is permissive for DNA translocation.
On the basis of the characterization of AutoN and NegC inhibitory roles, this conformational
change probably involves removal of both of these ATPase brakes (Manning and Peterson 2013).
Very recently, the C-terminal portion of ISWI emerged ad a relevant regulatory domain, playing an
important role in the nuclear import of the remodelling enzyme. While it has been previously shown
that the import of hSNF2H, one of the human ISWI homolog [ref], to the nucleus is controlled by
the accessory subunits of the complex (Sheu, Choi et al. 2008; Lan, Ui et al. 2010), in a very recent
study I has been shown that the nuclear import of S. cerevisiae Isw1 is mediated by a specific
nuclear localization signal (NLS) located at the end of the C-terminal partion (aa10079-1105) [ref].
In vitro binding assay of Isw1-NLS to importin- revealed that the nuclear translocation of Isw1 is
mediated by the classical import pathway. Moreover this mechanism was recognized as the solely
regulator of the remodeler nuclear translocation in vivo. Interestingly, similar nuclear localization
motif were identified in silico in ISWI orthologues of higher eukaryotes, suggesting that the Ctermini of the ISWI family proteins play an important role in their nuclear import (Vasicova,
Stradalova et al. 2013).
(2) ISWI chromatin remodelers regulation by protein-protein interaction (add Fig)
The enzymatic activity of ISWI chromatin remodelling complexes resides within their catalytic
ATPase subunit, but its associated subunits can modulate its activity therefore representing an
additional level of regulation of ISWI chromatin remodelling reactions. Since the discovery that
ISWI alone, out if the context of its associated subunits, has nucleosome remodelling activity
(Corona et al Mol cell 1999), at least two principal roles have been recognized for the accessory
subunits: (1) the modulation of nucleosome remodelling reactions and(2) the targeting of the
remodeling complex to the specific chromatin regions.
The first subunits able to regulate ISWI nucleosome remodelling activity to be identified were
Drosophila ACF1 and NURF301. Both ACF1 and NURF301 can modulate ISWI enzymatic
functions via their PHD finger domains that provide an anchor point to the nucleosome (Aasland,
Gibson et al. 1995; Eberharter, Vetter et al. 2004; Strohner, Wachsmuth et al. 2005; Wysocka,
Swigut et al. 2006). In particular, in the ACF and CHRAC complexes, the ACF1 subunit strongly
increases the ability of ISWI to assemble chromatin (Ito, Levenstein et al. 1999), and its
nucleosome sliding efficiency (Eberharter, Ferrari et al. 2001; Eberharter, Vetter et al. 2004). The
association of ISWI with ACF1 or NURF301 subunits is also able to determine the biochemical
properties of the ACF/CHRAC and NURF complexes. In fact, while ISWI alone catalyzes the
movement of a nucleosome toward the end of short DNA fragment, the ACF complex catalyzes the
movement of nucleosome toward the central portion of the same DNA fragment (Langst, Bonte et
al. 1999; Brehm, Langst et al. 2000; Eberharter, Ferrari et al. 2001). Similarly, in the NURF
complex, the NURF301 subunit modifies the intrinsic nucleosome mobilization proprieties of ISWI
and interacts with sequence-specific transcription factors, targeting NURF complex to specific
genes (Xiao, Sandaltzopoulos et al. 2001). In a similar way, also the non-catalytic subunits
associated with human SNF2H complexes (hACF, hRSC, hCHRAC and WICH) regulate SNF2H
ATPase ability to interact and remodel nucleosomes through their interaction with the linker DNA
emerging from nucleosome (He, Fan et al. 2008). The regulative role played by the accessory
subunit of ISWI complexes was recently also described for the novel evolutionary conserved ISWIcontaining complex ToRC. In ToRC complex all three subunits (TIP5/tou, ISWI, CtBP) are indeed
required for its maximal biochemical activity (Emelyanov, Vershilova et al. 2012).
Regulation by histones and post-translational modifications (add Fig)
Histone modifications
Histone tail domains are targeted by modifying enzymes responsible for their methylation,
acetylation, phosphorylation, ADP-ribosylation, and ubiquitination (Wu and Grunstein 2000;
Berger 2002; Bannister and Kouzarides 2011). Histone modifications not only directly regulate
chromatin structure by changing the interaction between the octamer and the DNA, but most
importantly by regulating remodelling enzymes chromatin targeting (Strahl and Allis 2000). The
ability to recognize histone modifications constitutes an integral part of all ATP-dependent
chromatin complexes that may either help the targeting of the enzymes to particular genomic sites
and/or modulate their activities. Particularly, the ISWI ATPase and its regulatory subunits posses
dedicated domains that specifically interact with unmodified and modified histone tails. In fact, one
of the peculiarities of ISWI remodelling enzymes is that they require the binding of H4 tail for
substrate recognition and efficient remodelling activity. Many studies in flies highlighted that the
DNA-bound basic patch of H4 is an epitope specifically bound by the SANT domain in ISWI
ATPase and that the state of acetylation of adjacent lysine residues, as K12 and K16, can negatively
influence the remodeler functions, like in the case of dNURF complex (Clapier, Langst et al. 2001;
Hamiche, Kang et al. 2001; Clapier, Nightingale et al. 2002; Corona, Clapier et al. 2002). Also in
yeast it has been demonstrated that the remodelling activity of Iswi2 is influenced by acetylation of
H4K16. This modification indeed decreases the catalytic rate of ATP hydrolysis, confirming that
unmodified H4 tail acts as an allosteric activator of the ATPase (Ferreira, Flaus et al. 2007) that is
important both for chromatin compaction and nucleosome remodelling by ISWI (Zhou, Feng et al.
2012). Furthermore, the ISWI containing complexes can also recognize the methylated histones
thanks the PHD finger domain present in the ISWI associated subunits. For example, the
trimethylated H3K4 is a histone post-translational modification with a regulatory role in the
recruitment of ISWI complexes. This substrate is bound by the PHD finger domain in BPTF subunit
of NURF complex (Wysocka, Swigut et al. 2006). Also in yeast, it has been shown that di- or trimethylation of the histone H3K4 is specifically required for the recruitment of Isw1 and for the
correct repositioning of RNA pol II in the coding regions (Santos-Rosa, Schneider et al. 2003). In
addition, regulatory roles regarding the phosphorylation of histones were also highlighted. In
Xenopus laevis there are evidences that xISWI complexes regulation during mitosis is under the
control of the INCENP-aurora B kinase complex that phosphorylates serine 10 of histone H3
(MacCallum, Losada et al. 2002).
Histone variants
ISWI remodelers recognize the modified histone tails in nucleosomes, as well as the globular
regions of the histone proteins. Besides the canonical core histones, there are several histone
variants that are incorporated into chromatin in a regulated manner and several classes of
chromatin remodelers, including ISWI subfamily, are known to be involved in incorporation and
stabilization of histone variants into the core of histonic octamer (Mizuguchi, Shen et al. 2004;
Konev, Tribus et al. 2007; Okada, Okawa et al. 2009; Perpelescu, Nozaki et al. 2009). Particularly,
H2A.Z, an H2A variant shown to be enriched at transcriptional control regions, it has been found to
increase the nucleosome activity of the hISWI (sostituire con SNF2h ? o Snf2l ? qual’e’
coinvolta ?) in vitro (Goldman, Garlick et al. 2010). Another works conducted in vivo on hRSF,
demonstrated that this remodeler is able to govern the replacement of H2Av in the pathway of silent
chromatin formation (Hanai, Furuhashi et al. 2008). Contradictory data exist about the role of
macroH2A: whereas in some works it has been demonstrated that this variant specifically interferes
with ACF and SWI/SNF nucleosome remodelling (Angelov, Molla et al. 2003; Doyen, Montel et al.
2006) and in a recent study it was demonstrated that macroH2A has a negative effect on the
recruitment and remodelling activity only of SWI/SNF (Chang, Ferreira et al. 2008). Another
example of how histone variants can regulate ISWI remodeler mode of action is represented by
H2A.X variant. This non-canonical histone, bind strongly than H2A to WICH complex and it has
been shown to be important in its recruitment to DNA repair sites (Xiao, Li et al. 2009).
ISWI posttranslational modifications
A further regulatory strategy of ISWI chromatin remodelers involves the direct post-translational
modification of the enzyme by specific proteins such as histone acetyl-transferase and poly-ADPribose polymerase. While it has been extensive documented the fact that the Gcn5 protein acts as an
histone acetyltransferase by targeting the H3K14 (Wang, Mizzen et al. 1997), the pioneering work
of Ferreira and colleagues identified and characterized for the first time in vitro and in vivo the
acetylation of dISWI ATPase by GCN5 at the conserved lysine 753 located in the HAND domain.
This study and other unpublished observations mentioned within, suggested that the acetylation of
ISWI is an early development regulated process probably linked to the expression of selected
Drosophila genes (Ferreira, Eberharter et al. 2007).
Interestingly, in vivo and in vitro investigations demonstrated that dISWI is also target of the PARP
enzyme, an abundant nuclear protein that transfer ADP-ribose to proteins important for DNA
transcription, repair and for chromatin structure. ISWI –PARP interactions was detected for the first
time in an unbiased genetic screens aimed to identifying factors modifying phenotypes caused by
loss of ISWI function. These screens provided the first genetic interaction map of potential
regulators of ISWI in the higher eukaryote Drosophila melanogaster .(Burgio, La Rocca et al. 2008;
Arancio, Onorati et al. 2010). Parylated dISWI displays a reduction in both nucleosome binding
affinity and in ATPase activity. Further, parylated ISWI tends to dissociate from its chromatin
target sites, suggesting that Poly ADP-ribosylation counteracts ISWI functions, in vitro and in vivo
(Sala, La Rocca et al. 2008).
While the phosphorylation of ATPase subunit of the hSWI/SNF remodelling complex was the first
example of phospho-regulation of a remodeler to have been documented, a regulation of ISWI-type
chromatin remodeling complexes by phosphorylation has not yet been highlighted. Nevertheless
work conducted by Oya and collegues, documented that the mammalian WSTF protein, a subunit of
two chromatin remodelling complexes (SWI/SNF type WINAC and ISWI-type WHICH), is
specifically phosphorylated at serine 158 by the stimulation of MAPK cascade in vitro and in vivo.
This modification has been demonstrated to be fundamental in finely tuning the balance between
the two WSTF containing complexes, involved in various nuclear event (Oya, Yokoyama et al.
2009).
(4) Regulation of ISWI chromatin remodelling activity by nucleic acids (add Fig)
DNA
Both the ISWI ATPase motor protein and its associated subunits contain DNA-binding motifs.
Thus, this raises the question whether DNA sequence influences chromatin remodelling activity
catalyzed by ISWI. Numerous in vitro studies have shown that the DNA sequence and
conformation is relevant for the outcome of the remodelling reaction (Stockdale, Flaus et al. 2006;
Rippe, Schrader et al. 2007). For instance, the remodelling reaction of the ISWI-type complex ACF
requires a short DNA element, with high intrinsic curvature, that determine ACF-dependent
nucleosome position (Rippe, Schrader et al. 2007). Moreover, a recent work suggested a mechanism
by which the DNA sequence cooperates with human remodeler ACF to switch nucleosomes
between two different locally meaningful positions based on environmental stimuli (Partensky and
Narlikar 2009). The DNA sequence feature role on the ISWI chromatin remodelling activity was
recently suggested also by genome-wide studies (Moshkin, Chalkley et al. 2012). Moreover, motif
discovery analysis, based on ISWI-associated sequences, suggests that dISWI preferentially bind
specific DNA consensus motifs, supporting the potential regulatory role played by underlying DNA
sequence in the targeting of ISWI to specific chromatin loci (Sala, Toto et al. 2011).
Linker DNA also has an effect on the ISWI remodelling. Whereas previous work paid little
attention whether the length of extra-nucleosomal DNA could be an important factor for
remodelling activity, the ISWI subfamily remodelers were the first to have shown a strong
dependence on linker DNA length (Zofall, Persinger et al. 2004). In particular, a drammatic
reduction in ISWI catalytic activity and nucleosome binding it has been documented when the
linker DNA was shortened (Kagalwala, Glaus et al. 2004; Zofall, Persinger et al. 2004; Dang,
Kagalwala et al. 2006; Stockdale, Flaus et al. 2006; Yang, Madrid et al. 2006). These observations
highlighted that the ISWI ATPase makes more extensive contacts with the linker DNA when is in
an activated ATP state compared to the inactivated state. However, until now it remains unclear
which step of the ATPase hydrolysis cycle the flanking DNA participates in.
An additional level of complexity is to distinguish the direct and indirect effects of DNA.
Several subunits of ISWI complexes interact with linker DNA forming an integral part of the
machinery that modulate the binding and activity of the ISWI ATPase domain. In yIsw2 the
accessory subunit Itc1 extensively interacts with at least 53 bp of extranucleosomal DNA
(Kagalwala, Glaus et al. 2004).
In agreement with this, a very recent study conducted in yeast, suggested that enrichment of yIsw1
at nucleosome-depleted regions (NDRs) is favoured by the transcription factors. Particularly, in this
work Zentner et al. suggested that TFs binding generate extended linker DNA regions which
enabling an efficient association between yIsw1 and its binding site (Zentner, Tsukiyama et al.
2013). Similarly, dCHRAC and hCHRAC complexes contain two additional histone-fold proteins
which enhance sliding activity mediate by ACF, probably by binding and bending the DNA
emerging from the nucleosome (Kukimoto, Elderkin et al. 2004; McConnell, Gelbart et al. 2004;
Hartlepp, Fernandez-Tornero et al. 2005). A similar mechanism has been observed by the high
mobility group (HMG) proteins which cooperate with ISWI chromatin remodelling complexes in
the increase their capacity to bind nucleosomal DNA and enhance their sliding activity (Xiao,
Sandaltzopoulos et al. 2001; Bonaldi, Langst et al. 2002).
Therefore, since the ISWI nucleosome remodelling regulation involves the alteration of the flanking
DNA at and around the nucleosome and since the accessory subunits interact with DNA, discern
each role is very difficult.
RNA
Another possible regulatory role of ISWI could be ascribed to RNA molecules. Indeed RNA, as
DNA, may represent a binding signal for ISWI chromatin remodelers. One example has been
shown for NoRC remodelling complex interaction with RNA. The RNA-NoRC interaction has been
found to be crucial for targeting the chromatin-remodelling complex to the nucleolus (Mayer,
Neubert et al. 2008). Moreover in vivo and in vitro interaction between the ATPase Drosophila
(Onorati, Lazzaro et al.
2011). Further, very recently the miR-99a was found to regulate the expression of Snf2h altering the
efficiency of DNA repair (Mueller, Sun et al. 2013)
Conclusions
Despite the simplicity of the nucleosome spacing reaction catalized by ISWI, its activity is highly
regulated and essential to support a variety of nuclear reactions that need nucleosomal accessibility.
Genetic and biochemical studies have provided a wealth of data concerning the mechanisms of
regulation of ISWI in different model systems. Indeed, ISWI activity is regulated by a complex
network of cellular and nuclear factors, explaining and supporting the participation of ISWI in
variety of biological processes
Acknowledgments
References
Aasland, R., T. J. Gibson, et al. (1995). "The PHD finger: implications for chromatin-mediated
transcriptional regulation." Trends in biochemical sciences 20(2): 56-59.
Angelov, D., A. Molla, et al. (2003). "The histone variant macroH2A interferes with transcription
factor binding and SWI/SNF nucleosome remodeling." Mol Cell 11(4): 1033-1041.
Arancio, W., M. C. Onorati, et al. (2010). "The nucleosome remodeling factor ISWI functionally
interacts with an evolutionarily conserved network of cellular factors." Genetics 185(1):
129-140.
Bannister, A. J. and T. Kouzarides (2011). "Regulation of chromatin by histone modifications." Cell
research 21(3): 381-395.
Berger, S. L. (2002). "Histone modifications in transcriptional regulation." Current opinion in
genetics & development 12(2): 142-148.
Bonaldi, T., G. Langst, et al. (2002). "The DNA chaperone HMGB1 facilitates ACF/CHRACdependent nucleosome sliding." The EMBO journal 21(24): 6865-6873.
Boyer, L. A., M. R. Langer, et al. (2002). "Essential role for the SANT domain in the functioning of
multiple chromatin remodeling enzymes." Mol Cell 10(4): 935-942.
Boyer, L. A., R. R. Latek, et al. (2004). "The SANT domain: a unique histone-tail-binding
module?" Nat Rev Mol Cell Biol 5(2): 158-163.
Boyer, L. A., R. R. Latek, et al. (2004). "The SANT domain: a unique histone-tail-binding
module?" Nature reviews. Molecular cell biology 5(2): 158-163.
Brehm, A., G. Langst, et al. (2000). "dMi-2 and ISWI chromatin remodelling factors have distinct
nucleosome binding and mobilization properties." The EMBO journal 19(16): 4332-4341.
Burgio, G., G. La Rocca, et al. (2008). "Genetic identification of a network of factors that
functionally interact with the nucleosome remodeling ATPase ISWI." PLoS genetics 4(6):
e1000089.
Chang, E. Y., H. Ferreira, et al. (2008). "MacroH2A allows ATP-dependent chromatin remodeling
by SWI/SNF and ACF complexes but specifically reduces recruitment of SWI/SNF."
Biochemistry 47(51): 13726-13732.
Clapier, C. R. and B. R. Cairns (2012). "Regulation of ISWI involves inhibitory modules
antagonized by nucleosomal epitopes." Nature 492(7428): 280-284.
Clapier, C. R. and B. R. Cairns (2013). "Regulation of ISWI involves inhibitory modules
antagonized by nucleosomal epitopes." Nature 492(7428): 280-284.
Clapier, C. R., G. Langst, et al. (2001). "Critical role for the histone H4 N terminus in nucleosome
remodeling by ISWI." Mol Cell Biol 21(3): 875-883.
Clapier, C. R., K. P. Nightingale, et al. (2002). "A critical epitope for substrate recognition by the
nucleosome remodeling ATPase ISWI." Nucleic Acids Res 30(3): 649-655.
Corona, D. F., C. R. Clapier, et al. (2002). "Modulation of ISWI function by site-specific histone
acetylation." EMBO Rep 3(3): 242-247.
Corona, D. F., G. Langst, et al. (1999). "ISWI is an ATP-dependent nucleosome remodeling factor."
Molecular cell 3(2): 239-245.
Dang, W., M. N. Kagalwala, et al. (2006). "Regulation of ISW2 by concerted action of histone H4
tail and extranucleosomal DNA." Molecular and cellular biology 26(20): 7388-7396.
Doyen, C. M., F. Montel, et al. (2006). "Dissection of the unusual structural and functional
properties of the variant H2A.Bbd nucleosome." EMBO J 25(18): 4234-4244.
Eberharter, A., S. Ferrari, et al. (2001). "Acf1, the largest subunit of CHRAC, regulates ISWIinduced nucleosome remodelling." The EMBO journal 20(14): 3781-3788.
Eberharter, A., I. Vetter, et al. (2004). "ACF1 improves the effectiveness of nucleosome
mobilization by ISWI through PHD-histone contacts." The EMBO journal 23(20): 40294039.
Emelyanov, A. V., E. Vershilova, et al. (2012). "Identification and characterization of ToRC, a
novel ISWI-containing ATP-dependent chromatin assembly complex." Genes &
development 26(6): 603-614.
Erdel, F., J. Krug, et al. (2011). "Targeting chromatin remodelers: signals and search mechanisms."
Biochim Biophys Acta 1809(9): 497-508.
Ferreira, H., A. Flaus, et al. (2007). "Histone modifications influence the action of Snf2 family
remodelling enzymes by different mechanisms." J Mol Biol 374(3): 563-579.
Ferreira, R., A. Eberharter, et al. (2007). "Site-specific acetylation of ISWI by GCN5." BMC Mol
Biol 8: 73.
Goldman, J. A., J. D. Garlick, et al. (2010). "Chromatin remodeling by imitation switch (ISWI)
class ATP-dependent remodelers is stimulated by histone variant H2A.Z." J Biol Chem
285(7): 4645-4651.
Grune, T., J. Brzeski, et al. (2003). "Crystal structure and functional analysis of a nucleosome
recognition module of the remodeling factor ISWI." Mol Cell 12(2): 449-460.
Grune, T., J. Brzeski, et al. (2003). "Crystal structure and functional analysis of a nucleosome
recognition module of the remodeling factor ISWI." Molecular cell 12(2): 449-460.
Hamiche, A., J. G. Kang, et al. (2001). "Histone tails modulate nucleosome mobility and regulate
ATP-dependent nucleosome sliding by NURF." Proc Natl Acad Sci U S A 98(25): 1431614321.
Hanai, K., H. Furuhashi, et al. (2008). "RSF governs silent chromatin formation via histone H2Av
replacement." PLoS Genet 4(2): e1000011.
Hartlepp, K. F., C. Fernandez-Tornero, et al. (2005). "The histone fold subunits of Drosophila
CHRAC facilitate nucleosome sliding through dynamic DNA interactions." Molecular and
cellular biology 25(22): 9886-9896.
He, X., H. Y. Fan, et al. (2008). "Diverse regulation of SNF2h chromatin remodeling by
noncatalytic subunits." Biochemistry 47(27): 7025-7033.
Hota, S. K. and B. Bartholomew (2011). "Diversity of operation in ATP-dependent chromatin
remodelers." Biochimica et biophysica acta 1809(9): 476-487.
Hota, S. K., S. K. Bhardwaj, et al. (2013). "Nucleosome mobilization by ISW2 requires the
concerted action of the ATPase and SLIDE domains." Nature structural & molecular
biology 20(2): 222-229.
Ito, T., M. E. Levenstein, et al. (1999). "ACF consists of two subunits, Acf1 and ISWI, that function
cooperatively in the ATP-dependent catalysis of chromatin assembly." Genes &
development 13(12): 1529-1539.
Kagalwala, M. N., B. J. Glaus, et al. (2004). "Topography of the ISW2-nucleosome complex:
insights into nucleosome spacing and chromatin remodeling." The EMBO journal 23(10):
2092-2104.
Konev, A. Y., M. Tribus, et al. (2007). "CHD1 motor protein is required for deposition of histone
variant H3.3 into chromatin in vivo." Science 317(5841): 1087-1090.
Kukimoto, I., S. Elderkin, et al. (2004). "The histone-fold protein complex CHRAC-15/17 enhances
nucleosome sliding and assembly mediated by ACF." Molecular cell 13(2): 265-277.
Lan, L., A. Ui, et al. (2010). "The ACF1 complex is required for DNA double-strand break repair in
human cells." Molecular cell 40(6): 976-987.
Langst, G., E. J. Bonte, et al. (1999). "Nucleosome movement by CHRAC and ISWI without
disruption or trans-displacement of the histone octamer." Cell 97(7): 843-852.
MacCallum, D. E., A. Losada, et al. (2002). "ISWI remodeling complexes in Xenopus egg extracts:
identification as major chromosomal components that are regulated by INCENP-aurora B."
Mol Biol Cell 13(1): 25-39.
Manning, B. J. and C. L. Peterson (2013). "Releasing the brakes on a chromatin-remodeling
enzyme." Nature structural & molecular biology 20(1): 5-7.
Mayer, C., M. Neubert, et al. (2008). "The structure of NoRC-associated RNA is crucial for
targeting the chromatin remodelling complex NoRC to the nucleolus." EMBO reports 9(8):
774-780.
McConnell, A. D., M. E. Gelbart, et al. (2004). "Histone fold protein Dls1p is required for Isw2dependent chromatin remodeling in vivo." Molecular and cellular biology 24(7): 2605-2613.
Mizuguchi, G., X. Shen, et al. (2004). "ATP-driven exchange of histone H2AZ variant catalyzed by
SWR1 chromatin remodeling complex." Science 303(5656): 343-348.
Moshkin, Y. M., G. E. Chalkley, et al. (2012). "Remodelers organize cellular chromatin by
counteracting intrinsic histone-DNA sequence preferences in a class-specific manner."
Molecular and cellular biology 32(3): 675-688.
Mueller, A. C., D. Sun, et al. (2013). "The miR-99 family regulates the DNA damage response
through its target SNF2H." Oncogene 32(9): 1164-1172.
Mueller-Planitz, F., H. Klinker, et al. (2013). "The ATPase domain of ISWI is an autonomous
nucleosome remodeling machine." Nature structural & molecular biology 20(1): 82-89.
Okada, M., K. Okawa, et al. (2009). "CENP-H-containing complex facilitates centromere
deposition of CENP-A in cooperation with FACT and CHD1." Mol Biol Cell 20(18): 39863995.
Onorati, M. C., S. Lazzaro, et al. (2011). "The ISWI chromatin remodeler organizes the hsromega
ncRNA-containing omega speckle nuclear compartments." PLoS genetics 7(5): e1002096.
Oya, H., A. Yokoyama, et al. (2009). "Phosphorylation of Williams syndrome transcription factor
by MAPK induces a switching between two distinct chromatin remodeling complexes." J
Biol Chem 284(47): 32472-32482.
Partensky, P. D. and G. J. Narlikar (2009). "Chromatin remodelers act globally, sequence positions
nucleosomes locally." Journal of molecular biology 391(1): 12-25.
Perpelescu, M., N. Nozaki, et al. (2009). "Active establishment of centromeric CENP-A chromatin
by RSF complex." J Cell Biol 185(3): 397-407.
Rippe, K., A. Schrader, et al. (2007). "DNA sequence- and conformation-directed positioning of
nucleosomes by chromatin-remodeling complexes." Proceedings of the National Academy
of Sciences of the United States of America 104(40): 15635-15640.
Sala, A., G. La Rocca, et al. (2008). "The nucleosome-remodeling ATPase ISWI is regulated by
poly-ADP-ribosylation." PLoS Biol 6(10): e252.
Sala, A., M. Toto, et al. (2011). "Genome-wide characterization of chromatin binding and
nucleosome spacing activity of the nucleosome remodelling ATPase ISWI." The EMBO
journal 30(9): 1766-1777.
Santos-Rosa, H., R. Schneider, et al. (2003). "Methylation of histone H3 K4 mediates association of
the Isw1p ATPase with chromatin." Mol Cell 12(5): 1325-1332.
Sheu, J. J., J. H. Choi, et al. (2008). "The roles of human sucrose nonfermenting protein 2
homologue in the tumor-promoting functions of Rsf-1." Cancer research 68(11): 4050-4057.
Stockdale, C., A. Flaus, et al. (2006). "Analysis of nucleosome repositioning by yeast ISWI and
Chd1 chromatin remodeling complexes." The Journal of biological chemistry 281(24):
16279-16288.
Strahl, B. D. and C. D. Allis (2000). "The language of covalent histone modifications." Nature
403(6765): 41-45.
Strohner, R., M. Wachsmuth, et al. (2005). "A 'loop recapture' mechanism for ACF-dependent
nucleosome remodeling." Nature structural & molecular biology 12(8): 683-690.
Vasicova, P., V. Stradalova, et al. (2013). "Nuclear import of chromatin remodeler Isw1 is mediated
by atypical bipartite cNLS and classical import pathway." Traffic 14(2): 176-193.
Wang, L., C. Mizzen, et al. (1997). "Histone acetyltransferase activity is conserved between yeast
and human GCN5 and is required for complementation of growth and transcriptional
activation." Mol Cell Biol 17(1): 519-527.
Wolffe, A. P. and J. J. Hayes (1999). "Chromatin disruption and modification." Nucleic acids
research 27(3): 711-720.
Wu, J. and M. Grunstein (2000). "25 years after the nucleosome model: chromatin modifications."
Trends in biochemical sciences 25(12): 619-623.
Wysocka, J., T. Swigut, et al. (2006). "A PHD finger of NURF couples histone H3 lysine 4
trimethylation with chromatin remodelling." Nature 442(7098): 86-90.
Xiao, A., H. Li, et al. (2009). "WSTF regulates the H2A.X DNA damage response via a novel
tyrosine kinase activity." Nature 457(7225): 57-62.
Xiao, H., R. Sandaltzopoulos, et al. (2001). "Dual functions of largest NURF subunit NURF301 in
nucleosome sliding and transcription factor interactions." Molecular cell 8(3): 531-543.
Yang, J. G., T. S. Madrid, et al. (2006). "The chromatin-remodeling enzyme ACF is an ATPdependent DNA length sensor that regulates nucleosome spacing." Nature structural &
molecular biology 13(12): 1078-1083.
Zentner, G. E., T. Tsukiyama, et al. (2013). "ISWI and CHD chromatin remodelers bind promoters
but act in gene bodies." PLoS genetics 9(2): e1003317.
Zhou, B. R., H. Feng, et al. (2012). "Histone H4 K16Q mutation, an acetylation mimic, causes
structural disorder of its N-terminal basic patch in the nucleosome." J Mol Biol 421(1): 3037.
Zofall, M., J. Persinger, et al. (2004). "Functional role of extranucleosomal DNA and the entry site
of the nucleosome in chromatin remodeling by ISW2." Molecular and cellular biology
24(22): 10047-10057.