Download X chromosome inactivation- Review

r-RNA silencing
A. Introduction rRNA produced in nucleoli
 Recall function of rRNA- interact with proteins to produce
ribosomes for mRNA translation into proteins
Protein
mRNA
phetRNA
Ribosomal subunits
1. Large
2. Small
Nucleolar dominance- in interspecific cell hybrids,
only rRNA genes inherited from one parent are
transcribed
Background on rRNA silencing
Species B
• 1930s- observe loss Species A
of “secondary
constrictions”of
chromosomes in cell
hybrids
• One species is
dominant over other
• The constrictions are A dominant over B
the location of rRNA
arrays
Species C
B dominant over C
A dominant over C
Constriction point was
called nucleolus
organizer regions
“NOR”
NORs contains 100s to
1000s of copies of rRNA
genes
What is mechanisms of rRNA
inactivation?
• Two hypotheses
Hypothesis # 1- species-specific transcription factor
Evidence for- human rRNA promoter inactive in
mouse cell free extracts (and vice versa)
…but if add human SL1 protein, then murine
extracts will activate human promoter
Human cell
extracts
Mouse cell
extracts
+SL1
Human rRNA promoter
Reporter gene
Active
Silent
Active
Evidence against- Inactivation still occurs within some
crosses of same species. Thus- an unlikely model
What is mechanisms of rRNA
inactivation?
Hypothesis # 2- enhancer imbalance hypothesis
The organisms with the most enhancers binds up
all available transcription factors; hence, it is
only one that expresses rRNA genes
Transcription factor
Species #1
rRNA
rRNA
Active
Species #2
rRNA
rRNA
Silent
Evidence for: If introduce many copies of intergenic regions
from species #1 into species #2, then repress species #2
rRNA expression.
Evidence against: no differences in number of binding sites or
affinities of binding sites in plants has been observed
Chromosomal context is important
in rRNA silencing
Drosophila
X
X
NOR
ON
NOR
OFF
Dros. m.
Dros. s.
NOR1
ON
Ch7
NOR2
ON
Dros. m.
Dros. s.
Male
Ch6
NOR1
ON
X
NOR
OFF
NOR
ON
Female
Plants
Y
Ch6
NOR2
OFF
Translocation
NOR1
ON
NOR1
ON
Duplication
NOR1
ON
Chromosomal context is important
in rRNA silencing
Plants
Ch1
NOR1
OFF
Ch1
Ch1
Ch1
NOR2
ON
NOR2
ON
NOR1
ON
Rye
Wheat
Rye
Translocation
Wheat
Are methylation and/or histone
acetylation involved?
• Methylation- controverisal role due to
similar methylation in active and inactive
NORs
– But if demethyalate, activate silent rRNA genes
• Acetylation– Acetylase inhibitors activates silent rRNA
genes
Perhaps both methylation and acetylation contribute to
silencing rRNA genes