Download Diverse roles of the Mediator complex in plants

Diverse roles of the Mediator complex in plants
Brendan N. Kidd, David M. Cahill, John M. Manners, Peer M. Schenk and Kemal Kazan
Affiliations
School of Agriculture and Food Sciences, The University of Queensland, St Lucia, Queensland,
4072, Australia
School of Life and Environmental Sciences, Deakin University, Geelong, Victoria 3217,
Australia
Commonwealth Scientific and Industrial Research Organization Plant Industry, Queensland
Bioscience Precinct, St Lucia, Queensland, 4067, Australia
Abstract
Since its original discovery in yeast, the Mediator complex has been identified in a wide range of
organisms across the vast eukaryotic kingdom. Despite being experimentally purified from a
number of metazoan organisms, it wasn’t until 2007, thirteen years after its initial discovery, that
the Mediator complex was successfully isolated from plants. With a number of papers beginning
to emerge on the plant Mediator complex, this review aims to provide an overview of the diverse
functions that have been identified for individual plant Mediator subunits. In addition to
demonstrating roles in plant development, flowering, hormone signaling and biotic and abiotic
stress tolerance; recent findings have revealed an intriguing array of accessory functions for plant
Mediator subunits, including mRNA, miRNA and rRNA processing, as well as controlling DNA
and protein stability. These diverse activities expand on the known functions of the Mediator
complex and demonstrate the variety of information that can be gained from investigations into
the plant Mediator complex. Future directions for research into this multi-functional protein
complex will be discussed.
Keywords
Mediator complex, plant hormone signaling, abiotic, plant defense, transcription, microRNA
Insert Table of contents
Introduction
The act of transcription is an intricate process and is carried out by a large collection of proteins
working in synchrony. In eukaryotes, the major proteins involved during initiation of
transcription are the RNA polymerase II enzyme, the general transcription factors (GTFs), the
variety of trans-acting activators and repressors, and the Mediator complex. Prior to the
discovery of the Mediator complex, artificial transcription studies using RNA Pol II and five
GTFs purified from yeast, Saccharomyces cerevisiae, demonstrated that these proteins were the
minimum components required for performing transcription (Flanagan et al., 1991; Kim et al.,
1994*). However the artificial transcription systems could not support high levels of
transcription and resulted in “squelching” when two known transcriptional activators were added
to the system. The missing activity could be restored by the addition of a crude cell culture but
not by the addition of any of the previously known components of the transcription complex. The
subsequent isolation of approximately 20 proteins that were required to restore the transcriptional
activity was revealed and collectively termed the Mediator complex (Kim et al., 1994). In the
ensuing years, analyses of the Mediator complex have established its role as an important
component of eukaryotic transcription.
The Plant Mediator complex
Since its original discovery in yeast, the Mediator complex has since been found experimentally
and in silico in almost all eukaryotes (Boube et al., 2002; Bourbon, 2004; 2008 more refs). The
presence of the Mediator complex in plants had been suggested based on sequence homology
(Autran et al., 2002; Boube et al., 2002; Clay and Nelson, 2005; Gonzalez et al., 2007; Gurley et
al., book chapter 2007), however it wasn’t until 2007, thirteen years after its discovery in S.
cerevisiae, that the plant Mediator complex was successfully purified (Backstrom et al., 2007).
Twenty-one Mediator subunits were isolated from the model plant Arabidopsis thaliana that
were conserved between other eukaryotes as well as six subunits that appeared to be specific to
plants. In addition, six of the isolated proteins appeared to have paralogs in the Arabidopsis
genome, arising from a potential gene duplication event. Although twenty-one conserved
subunits were present in the Arabidopsis Mediator purifications, there appeared to be a number
of missing subunits, such as MED1, MED2, MED3, MED5, MED24, MED26, MED27, MED29
and MED30 subunits, as well as the MED12-MED13, CDK8 kinase and its partner cyclin
(CYC). The MED12 MED13 CDK8 CYC subunits form a detachable kinase module in the
Mediator complex. Although the kinase module wasn’t able to be purified with the Arabidopsis
Mediator complex, homologs to MED12, MED13 and CDK8 have been identified in A. thaliana
through sequence comparison (Wang and Chen, 2004; Gillmor et al., 2010; Ito et al., 2010). In
addition, Arabidopsis is known to have at least 30 cyclins, although the cyclin that specifically
interacts with CDK8 in Arabidopsis is yet to be identified (Wang and Chen, 2004).
The Plant Mediator complex versus other eukaryotic Mediator complexes
The discovery of the Mediator complex in plants, implicated a fresh batch of proteins that are
required for efficient co-ordination of the plant transcriptome. Individually the Mediator subunits
are expected to possess their own specific function within the complex, and already, a handful of
Mediator subunits have been shown to have important roles in distinct cellular processes. To
determine the possible functions of the remaining subunits, it is tempting to exploit the
functional information available from other relatively well characterized Mediator subunits.
However, at the sequence level, the similarity between plant Mediator complexes and other
eukaryotic Mediator complexes is quite low, with partial protein searches revealing at best
around 20-30% identity (Bäckström et al., 2007).
Interestingly, sequence homology between the Arabidopsis Mediator subunits and corresponding
proteins from other plants species is surprisingly high. A BlastP search with the full length
Arabidopsis MED25 protein sequence revealed matches with 66% identity in both grape (Vitis
vinifera) and poplar (Populus trichocarpa) (Báckstrom et al., 2007). Similarly, a search with the
Arabidopsis MED21 subunit reveals a match of 79% identity to a protein from P. trichocarpa
and 75% to a potential soybean homolog (Glycine max). Therefore, while the Arabidopsis
Mediator complex appears to have diverged significantly at the sequence level from the
metazoan and fungal Mediator complexes, it retains strong sequence conservation between
plants. Examples of conserved Mediator subunit function between plant species has been shown
in the literature with orthologues of the MED25 gene in wheat and the MED16 gene in rice being
able to complement the flowering and pathogen phenotypes of the med25 mutant, and the cold
and osmotic stress phenotypes of the med16 mutant in Arabidopsis, respectively (Kidd et al.,
2009; wathugala 2011).
However, despite significant differences in the primary sequence between plants and other
eukaryotic lineages, Bourbon, (2008) showed that Mediator subunits from very diverse phyla
could be identified using evolutionary conserved signature sequence motifs (SSMs). Using these
analyses, Bourbon (2008) identified all but two Mediator subunits in plants and all of the human
subunits in the distant amoeba Dictyostelium discoideum, suggesting that the Mediator complex
is more evolutionarily conserved than first thought. In addition, Bourbon, (2008) suggested that
the yeast specific subunits, MED2, MED3 and MED5, may correspond to the metazoan specific
MED24, MED27 and MED29 and the plant specific subunits MED32, MED27 and MED33a/b
identified in Arabidopsis. Following this new interpretation, it appears that all of the conserved
Mediator subunits, with the exception of MED1 and MED26, are present in Arabidopsis. With
an increased confidence in the level of conservation between subunits, this suggests that
understanding the function of the individual plant subunits may provide information for all
Mediator complexes. While at the primary sequence level, Mediator subunits may have diverged
through evolution, at the secondary level many subunits still retain core domains that are
necessary for Mediator or transcription factor interaction, and it is these regions that could be
investigated to provide further information regarding subunit function (Backstrom et al., 2007;
Bourbon et al., 2008). For instance, the MED25 protein contains the structurally conserved Von
Willebrand factor type A (vWF Pfam · PF00093) domain in its amino terminus, and towards the
carboxyl terminus, contains a conserved activation domain required for interaction with various
transcriptional activators in plants and humans (refs mittler etc). In the following section we will
discuss some of the functions and phenotypes currently identified for the Mediator subunits
identified in Arabidopsis and discuss what can be learned from the plant Mediator complex.
The Function of the Plant Mediator complex
To the best of our knowledge, fifteen plant Mediator subunits have a published phenotype or
function, while the rest are yet to be characterized (Table 1). Some of the physiological processes
that Mediator subunits were found to regulate include the response to abiotic and biotic stress, as
well as developmental control, flowering, and fertility. Other subunits provide essential nuclear
functions such as DNA helicase activity, or have roles in RNA processing such as mRNA
splicing or rRNA methylation. In addition, a recent publication also reported an exciting role for
the Mediator complex in non-coding RNA production (Kim et al., 2011). The characterization of
these genes as subunits of the Mediator complex demonstrates the important and diverse roles
that individual subunits can possess. The recent progress in defining the function of a selection of
the plant Mediator subunits is reviewed below. Please note that some Mediator subunits have
been functionally characterized before their formal identifications as Mediator subunits and
therefore, these particular subunits are also known under different names.
Development
The Mediator complex has been shown to be essential for growth and development in a variety
of organisms (refs). It is therefore expected that the plant Mediator complex would also exhibit
essential roles in development. One subunit currently identified as having a function in
development is the MED14 subunit. Prior to its identification as a Mediator subunit, the
STRUWWELPETER (SWP) gene was known to affect cell number and shoot meristem
development. Transfer DNA (T-DNA) insertion mutations in the SWP gene resulted in dwarf
plants with delayed flowering and an un-organized meristem (Autran et al., 2002). Based on
sequence homology to the yeast and human MED14, Autran et al., (2002) hypothesized that the
SWP gene was a component of the Mediator complex and that it possibly interacts with histone
modifying complexes. This prediction was confirmed five years later with the discovery that
SWP was indeed MED14 of the Arabidopsis Mediator complex and that through interactions
with the co-repressor LEUNIG (LUG), it was also able to recruit HISTONE DEACETYLASE
19 (HDAC19) (Backstrom et al., 2007; Gonzalez et al., 2007). The LUG repressor was also
shown to interact with the CDK8 subunit (Gonzalez et al., 2007). In addition, MED14 was
shown to affect the expression of the Arabidopsis splicing factors SMP1 and SMP2, mutants of
which display similar phenotypes to med14 and are essential for proper development (Clay and
Nelson, 2005). The interaction between MED14 and the two splicing factors still needs to be
elucidated but further investigation could provide clues regarding the function of MED14 in
controlling development.
In addition to MED14, mutants in the kinase module of the Mediator complex MED12, MED13
and CDK8 all show developmental phenotypes due to altered cell differentiation (Wang and
Chen, 2004; Gillmore et al., 2010; Ito et al., 2010). The med12 and med13 mutants are affected
in the transition from globular to heart stage embryos due to a delay in the expression of
KANADI1 and KANADI2 transcription factors early on in development (Gillmor et al., 2010).
The effect of the med13 mutation on cell differentiation has also been explained by a defect in
response to the hormone auxin (Ito et al., 2010). The CDK8 mutant otherwise known as hen3
also shows defects in cell differentiation which leads to altered development of floral organs in
this mutant (Wang and Chen, 2004).
The role of the multifunctional MED25 subunit in flowering, hormone and stress pathways
In addition to controlling plant development, the Mediator complex has been shown to be
responsible for the regulation of a variety of physiological processes such as flowering time,
hormone signaling pathways, and ability of plants to respond to biotic and abiotic stress. One
subunit that has recently been shown to integrate all of these functions is the MED25 subunit.
The MED25 gene, also known as PFT1, was originally described as a regulator of the adaptive
process known as shade avoidance, and was suggested to promote flowering in response to
changes in light quality (Cerdán and Chory, 2003). An additional role for MED25/PFT1 in
pathogen defense has been shown with med25/pft1 mutants having increased susceptibility to the
leaf infecting fungal pathogens Alternaria brassicicola and Botrytis cinerea and increased
resistance to the root infecting fungal pathogen, Fusarium oxysporum (Kidd et al., 2009). The
med25/pft1 mutant also showed reduced transcription of a number of plant defense genes,
particularly those responsive to the plant hormone, jasmonate (JA) (Kidd et al., 2009). Recently,
an interaction of MED25/PFT1 with eight individual transcription factors has been shown using
a high-throughput yeast-2-hybrid library (Ou et al., 2011). Three of the transcription factors
identified were able to bind to the promoter of PLANT DEFENSIN1.2 (PDF1.2) gene, a
commonly used marker for the JA hormone pathway (Ou et al., 2011). A failed interaction with
these transcription factors in the med25/pft1 mutant could potentially explain why JA-associated
gene expression was reduced.
Recent work has revealed an additional three transcription factors that interact with
MED25/PFT1 (Elving et al 2011). Two of the transcription factors that were identified, ZFHD1
and DREB2A, have published roles in abiotic stress tolerance (Tran 06 Sakuma 06). The authors
were able to show that med25/pft1 mutant plants also displayed alterations in both drought and
salt stress; however the increased drought resistance phenotype of med25/pft1 was in opposition
to the increased drought sensitivity of the two transcription factors mutants (Elving et al 11).
Nevertheless, these findings demonstrate the versatility of the MED25/PFT1 subunit in
regulating multiple pathways, from hormone signaling and flowering to abiotic and biotic stress
responses. However, the MED25/PFT1 subunit is not the only Mediator subunit to control these
pathways and a number of other Mediator subunits have published roles in flowering time
(MED8, MED17, MED18, MED20A; Kidd et al., 2009, Kim et al., 2011), biotic stress (MED8,
MED21; Dhawan et al., 2009 Kidd et al., 2009) or abiotic stress (MED16 Knight et al 2008 2009
2011).
A new role for Mediator in miRNA biogenesis and genome defense
The function of the Mediator complex is most often associated with RNA Pol II and the
regulation of protein coding genes. However mRNA from protein coding genes represents only a
small fraction of the RNA that is transcribed in plants and other eukaryotes. In light of this, a
recent paper investigated the role of Mediator complex in small and long non-coding RNA
production to see whether the Mediator complex is also required for non-coding RNA
biogenesis. The authors discovered that three Mediator subunit mutants, med17, med18 and
med20a, displayed reduced levels of plant miRNAs (Kim et al., 2011). In addition RNA Pol II
occupancy was found to be reduced at miRNA promoters in the med20a mutant, suggesting that
a functional Mediator complex is required for recruitment of RNA Pol II to the promoter regions
of miRNA genes. Kim et al., (2011) also found that the Mediator complex may be involved in
silencing of transposons and repeat sequences. A number of elements that normally undergo
siRNA mediated transcriptional gene silencing were de-repressed in med17, med18 and med20a.
The true extent of Mediator involvement in these processes still needs to be further investigated;
however these findings demonstrate an exciting role of the Mediator complex beyond the
transcription of protein coding genes. One intriguing hypothesis suggested by the authors is that
Mediator may co-operate with other RNA polymerases in plants, such as RNA Pol V, to carry
out transcriptional gene silencing. Interestingly, another study in Arabidopsis managed to copurify the MED36 subunit with the largest subunit of Pol V (Huang et al., 2009). This finding
perhaps suggests that the plant Mediator may function with other RNA polymerases directly, or
through the interaction of common accessory proteins. Overall these investigations expand our
knowledge of the Mediator complex’s abilities, and also demonstrate some of the exciting
insights that have been gained from studying the plant Mediator complex.
Mediator as a scaffold for accessory proteins or bonafide multifunctional Mediator
subunits?
Following on from the recent finding of Mediator in noncoding RNA biogenesis, the discovery
of Backstrom et al (2007) of six plant specific subunits revealed a number of genes that possess
important and diverse roles in the nucleus and nucleolus. For example, the MED34 subunit has
been identified as a DNA helicase, while the MED35 and MED36 have been associated with
mRNA and rRNA processing. Interestingly the identification of MED37 revealed a role outside
of the nucleus and has been found to encode a HSP70 family member previously shown to
localize to the endoplasmic reticulum. Here we summarize some of these functions and discuss
their inclusion as subunits of the Mediator complex.
Backstrom et al., (2007) found the Arabidopsis gene, At1g44910, in two Mediator purifications
and thus annotated it as a putative plant specific MED35 subunit. Prior to its identification as the
MED35 subunit, the gene was annotated as an unknown protein with homology to the human
Transcription elongation factor (TCERG1), previously known as COACTIVATOR OF 150kDA
(CA150) (Backstrom et al., 2007). More recently, Kang et al., (2009) identified the MED35 gene
as being one of three Arabidopsis genes similar to the S. cerevisiae PRP40 (PRE mRNA
PROCESSING PROTEIN 40) gene. Both the S. cerevisiae PRP40 gene as well as the human
CA150 gene have been shown to bind to the C terminal domain (CTD) of RNA Pol II and are
involved in the splicing of pre-mRNA (Kao and Siliciano, 1996; Morris and Greenleaf, 2000;
Pearson et al., 2008). Binding analyses using yeast two-hybrid and far Western blotting revealed
that all three Arabidopsis PRP40 proteins, including MED35, were able to bind to the CTD of
RNA Pol II, suggesting a conserved function between plants and humans (Kang et al., 2009).
Interestingly Sune et al., (1997) showed that human TCERG1 co-precipitated with the human
MED21 subunit, even though TCERG1 has not yet been considered to encode a Mediator
subunit in humans.
In addition, the gene identified as MED34 has been identified as a homolog of the human RecQ
DNA helicases and is one of seven RecQ homologues in plants (Kobbe et al., 2008). RecQ
helicases play an important role in maintaining genome stability by unwinding recombinogenic
structures and the Arabidopsis MED34 was shown to possess the ability to disrupt both D-loop
and Holliday junctions in vitro (Kobbe et al., 2008).
Finally, the MED36 subunit has been shown to encode a Fibrillarin which is involved in
processing rRNA. In eukaryotes, rRNA is transcribed by RNA Pol I as a large pre-cursor
fragment that is then cleaved to generate the individual 5.8S, 18S and 20S fragments. Together
with other nucleolar proteins and snoRNA (small nucleolar RNA), the Fibrillarin gene is
required for the early cleavage steps of the large rRNA precursor as well as proper ribosome
assembly (Tollervey et al 1993).
These findings raise the question of whether these proteins are bona fide Mediator subunits, or
whether they are accessory proteins that are recruited to the Mediator complex. All of the
proteins mentioned in this review were isolated from two separate Mediator preparations using
antibodies against the Arabidopsis MED2/32 and MED6 subunits, suggesting that they can be
consistently found attached to the Mediator complex. It is now becoming apparent that the
Mediator complex acts not just as an adapter between transcription factors and Pol II, but also
acts as a scaffold for a wide range of accessory functions. This has been demonstrated well in
other organisms with the Mediator complex interacting with the cohesion proteins and chromatin
modifiers (black et al 2006; Kagey et al 2010) amongst others, and in plants it is now apparent
that Mediator is involved in controlling DNA stability through a RecQ helicase, processing of
mRNA and rRNA as well as potentially protein stability through the function of MED37 as a
HSP70 chaperone protein. These findings further corroborate the role of the Mediator complex
as a docking site for a diverse range of nuclear machinery.
Current examples of conserved function between Mediator subunits
As well as providing intriguing new clues regarding Mediator function, investigation into the
plant Mediator has revealed a number of similarities between plant and other eukaryotic
Mediator function. The Arabidopsis MED14 was found to interact with the Arabidopsis corepressor LUG and this discovery was made based on the knowledge that yeast MED14/RGR1
interacts with TUP1, a homolog of LUG in yeast (Conlan et al., 1999; Gonzalez et al., 2007).
The LUG repressor also interacted with the CDK8 subunit, which has previously been associated
with transcriptional repression (ref). These findings suggest that co-repressors such as LUG and
TUP1 may potentially recruit a repressive form of Mediator complex to facilitate target gene
repression.
As mentioned above the MED12, MED13 and CDK8 subunits all show roles in cell
differentiation and development in Arabidopsis. MED12, MED13, CDK8 and its cyclin partner
have been shown to form a sub-module in the Mediator complex (ref), yet despite this, the
function of CDK8 compared to MED12 and MED13 in development appears to be different,
suggesting separate functions within the module. Similarly, the MED12, MED13, CDK8 and
CYC sub-module has been shown to be important for development in mice and Drosophila.
Interestingly in Drosophila the MED12 and MED13 subunits also displayed different
developmental phenotypes to those of the CDK8-CYC pair (Loncle et al., 2007), which suggests
the separate roles of MED12-13 and the CDK8-CYC pair may be evolutionarily conserved. How
the four subunit module conveys different phenotypes and whether this is related to its function
as a RNA Pol II CTD kinase remains unknown.
Interestingly, the Med25 subunit, which controls multiple disease, stress and development
processes in plants, is also involved in related processes in other eukaryotes. Comparable to the
attenuation of plant defense genes in the Arabidopsis med25 mutant, RNA interference mediated
suppression of Drosophila MED25 resulted in attenuated induction of the antibacterial peptide
attacin in response to lipopolysaccharide treatment (Kim et al., 2004). In addition, the human
MED25 has been shown to be the cellular target of a number of viral activators such as VP16,
the well-studied activator of herpes simplex virus (Mittler et al., 2003; Yang et al., 2004), Lana-1
the activator from the Kaposi Sarcoma associated herpes virus (Roupeliera et al., 2010), and
IE62, the activator from the closely related Varicella Zoster virus, the virus responsible for
chicken pox and shingles (Yang et al., 2008; Yamamoto et al., 2009). As the MED25 subunit is
not found in yeast, the above examples could suggest that the MED25 protein may have evolved
in higher eukaryotes to function as an integrator within the Mediator complex for the
transcriptional control of pathogen responses.
However, in addition to the defense functions, MED25 has been shown to be involved in
Retinoic acid signaling, xenobiotic and lipid metabolism, cranofacial development as well as the
motor and sensory neuropathy Charcot Marie Tooth Disease (refs). These diverse functions in
both pathogen defense and hormone and developmental control highlight the varied processes
that individual Mediator subunits can regulate. Further investigation into Mediator subunit
function may reveal whether this multi-functionality of the MED25 subunit is the exception or
the rule.
The way forward
Despite only recently been discovered in plants, the characterization of the Mediator complex
has proceeded in leaps and bounds. The above examples are a selection of the most recent
findings that the plant Mediator complex has provided. The identification of the roles of the
remaining Mediator subunits will undoubtedly follow and will continue to provide new insights
into the regulatory control of eukaryotic transcription. Perhaps of most interest to plant scientists
is how the Mediator complex regulates specific plant processes. Determining which activators
and repressors each subunit interacts with will be crucial to identifying their involvement in
different signaling pathways. Related to this is the incredible ability of the Mediator complex to
integrate the thousands of transcription factors that are present in eukaryotes. For example, from
the recent identification of the MED25 interacting proteins in Arabidopsis, it is apparent that
multiple members from a number of different transcription factor families are able to interact
with the MED25 interaction domain. The recent structural determination of the human MED25
interaction domain (Vojnic Milbradt) as well as future studies of conserved domains in the other
Mediator subunits could provide clues to how Mediator subunits may cope with the integration
of multiple signaling pathways and protein interactions.
To add even greater complexity, the plant and human Mediator complex has been shown to
contain subunit paralogs, most likely due to genome duplication events. In addition, many
important crop plants have polyploid genomes and would therefore contain multiple genes
encoding subunits of the Mediator complex. Whether paralogous or homeologous, Mediator
subunits are incorporated into different Mediator complexes, or instead exist as a dynamic fusion
of different subunits remains to be further elucidated. Subunits of the Mediator complex have
been shown to exist in substochiometric amounts within the complex and therefore different
subunits be recruited to the complex during developmental or in different tissues as required
(sato 2004 zhang 2005 mittler).
In addition, the newly identified roles of the Mediator complex in non-coding RNA production
as well as its roles in rRNA processing open up the involvement of Mediator in alternative
nuclear functions. It is possible that the Mediator complex is involved in the majority of
transcriptional processes; from DNA access, to activator binding, RNA polymerase recruitment,
right through to elongation and post transcriptional control. There is the potential for more
discoveries like this through further investigation of the Mediator complex and quite possibly,
these investigations will help shed light on the entire transcriptional process.
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Arabidopsis MED25 Integrates Multiple Signals through Interactions with Different
Mediator
Mediator
Activato
Activato
MED25
AP2
/ER
MED25
DRE
B2A
RNA
Pol II
RNA
Pol II
Gene
Gene
F
GTFs
GTFs
Jasmonate signalling
Biotic
Mediator
Activato
Activato
MED25
ZHF
D1
Salt Tolerance
Abiotic
Mediator
MED25
MY
B-
RNA
Pol II
RNA
Pol II
Gene
GTFs
Abiotic
F
Gene
F
Salt Tolerance
GTFs
Abiotic
F
Salt Tolerance
Table 1. Known Mediator subunits in Arabidopsis and their functions deduced from
mutant analysis
MED Subunit
MED2/MED32
MED3/MED27
MED4
MED5a/MED33a
MED5b/MED33b
REDUCED EPIDERMAL
FLUORESCENCE 4 (REF4).
MED6
MED7a
MED7b
MED8
SETH10
AGI locus
At1g11760
At3g09180
At5g02850
At3g23590
At2g48110
At3g21350
At5g03220
At5g03500
At2g03070
MED9
MED10a
MED10b
MED11
MED12
CENTER CITY (CCT)
CRYPTIC PRECOCIOUS
(CRP)
MED13
GRAND CENTRAL (GCT)
MACCHI-BOU 2 (MAB2)
CDK8
HUA ENHANCER3 (HEN3)
MED14
STRUWWELPETER (SWP)
At1g55080
At5g41910
At1g26665
At3g01435
At4g00450
MED15
MED16
SENSITIVE TO FREEZING6
(SFR6)
At1g15780
At4g04920
MED17
At5g20170
MED18
At2g22370
MED19a
MED19b
MED20a
At5g12230
MED20b
MED21
At4g09070
At4g04780
MED22a
MED22b
MED23
At1g16430
At1g07950
At1g23230
At1g55325
At3g04740
At2g28230
Function/Mutant Phenotypes
Unknown
Unknown
Unknown
Unknown
Required for uncompromised accumulation of phenylpropanoid-pathway
partially dwarfed and accumulates reduced quantities of all phenylpropan
(Stout et al., 2008)
Unknown
Unknown
Unknown
Regulates plant defense and flower development/flowering. med8/seth10
altered pathogen responses (Kidd et al., 2009). med8/seth10 has reduced c
slower pollen tube growth (Lalanne et al., 2004)
Unknown
Unknown
Unknown
Unknown
Required for correct embryo development. med12/cct affects the timing o
al., 2010)
MED13/GCT/MAB2 is required for embryo development. med13/gct/ma
patterning (Ito et al., 2010; Gillmor et al., 2010)
CDK8/HEN3 is required for correct floral organ development and interac
LEUNIG (LUG) (wang and chen, Gonzalez)
MED14/SWP regulates development. med14/swp possesses reduced cell n
shoot apical meristem. Interacts with the co-repressor LUG (Autran et al.,
Gonzalez et al., 2007)
Unknown
Regulates cold and osmotic stress responses. Mutant is impaired in these p
1996; Boyce et al., 2003). MED16/SFR6 potentially interacts with CBF (C
transcription factors to activate COR (COLD ON REGULATED) gene ex
2008; 2009)
MED17 regulates development and non coding RNA production. Mutant
developmental phenotypes to med20a and displays reduced miRNA leve
MED18 regulates development and non coding RNA production. Mutant
developmental phenotypes to med20a and displays reduced miRNA leve
Unknown
Unknown
MED20a regulates development and non coding RNA production. med20
altered leaf phyllotaxis and is important for non-coding RNA biogenesis (
Unknown
Regulates development and plant defense and interacts with the E3 ligase
MONOUBIQUITINATION1). Insertion mutants are embryo lethal howev
susceptibility to necrotrophic plant pathogens (Dhawan et al., 2009)
Unknown
Unknown
Unknown
MED25
PHYTOCHROME AND
FLOWERING TIME 1 (PFT1)
At1g25540
MED28
MED31
MED34
RECQ HELICASE2 (RECQ2)
At3g52860
At5g19910
At1g31360
MED35
PRE mRNA PROCESSING40a
(PRP40a)
MED36
FIBRILLARIN2 (FIB2)
At1g44910
MED37a
BINDING PROTEIN1 (BIP1)
At5g28540
At4g25630
Is involved in flowering, as well as biotic and abiotic stress responses. me
flowering, altered JA gene expression and pathogen responses (Cerdan an
al., 2008; Kidd et al., 2009) It has also been shown to regulate drought an
interact with several transcription factors (Ou et al., 2011; Elfving et al., 2
Unknown
Unknown
Encodes a dNTP-dependent 3'->5' DNA helicase important for genome st
disrupt D loop structures and mediate branch migration of Holliday juncti
et al., 2009)
Similar to yeast PRP40 and was shown to bind the carboxyl-terminal dom
subunit of RNA polymerase II. (Kang et al., 2009)
MED36/FIB2 encodes a fibrillarin, a key nucleolar protein in eukaryotes
small nucleolar RNAs to regulate methylation and cleavage of rRNA (Bar
with and is methylated by histone methyltransferases AtPRMT1a and AtP
copurifies with Pol V (Huang et al., 2009)
Encodes the luminal binding protein BIP1, a member of the HSP70 family
Ig binding protein. In Arabidopsis BIP1 interacts with the brassinosteroid
2007; hong et al., 2008) and bip1/bip2 double mutants are defective in po
development (Maruyama et al., 2010)