Polycomb, trithorax, and maintenance of gene expression

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Polycomb, trithorax, and maintenance of gene
expression
Early development
OFF
Maternal, Gap, Pair-rule, Segment polarity
ON
Establishment of patterns
Ubx
ON
OFF
Maintenance phase
trithorax-Group
Polycomb-Group
Transmission of pattern after disappearance of
early factors
ON
OFF
Update December 2004
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Action of PcG and trxG complexes on chromatin
trxG
Nucleosome remodeling (BRM complex)
ON
Ac
Maintenance of active states (open chromatin)
Histone acetylation and methylation (TAC1 and
ASH1 complexes)
Me K4 H3
Target gene
PRE
PcG
OFF
Me K27 H3
Deacetylation and methylation (ESC-E(Z) complex)
Maintenance of repressed states (compact
chromatin)
- Chromatin compaction - H2A Ubiquitination (PRC1
complex)
Ub H2A
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Histone H3 methylation and Polycomb
Pc
H3 K9 triMe
Merge
Data from Ringrose et al. (2004) Mol. Cell 16,
641
Merge
Pc
H3 K27 triMe
There is a strong but not absolute correlation
between trimethylation of K27 (and K9)
trimethylation and Polycomb recruitment at target
loci. i.e. there is more to Pc recruitment
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What do  Polycomb  proteins do to chromatin
? 1. Condensation
Recombinant PC-containing complexes can condense
an array of 12 nucleosomes in vitro Condensation
requires PSC (not PH) protein, and involves
histones but does not necessitate histone tails
Data from Francis et al. (2004), Science 306,
1574
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What do  Polycomb  proteins do to chromatin
? 2. H2A Ubiquitination
Data from Wang et al. (2004) Nature 431, 873
Purified human PRC1-type complexes can
Ubiquitinate H2A in vitro, and the drosophila
counterpart of the same complex induces a
dRing-dependent H2A Ub at the Ubx PcG target gene
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Features of PREs and TREs, and examples of how
they are studied in drosophila
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1. Example of PcG-dependent spatial specific
silencing of homeotic genes
bxd5.1 UbxlacZ reporter construct
Bxd 5.1 PRE
Ubx prom
LacZ
mini-white
Silencing of a Ubx-lacZ reporter mimicking the wt
behaviour of the Ubx gene, which is silenced in
parasegments 1 to 5
PcG dependent derepression of a Ubx-lacZ reporter
in embryonic territories where it is normally
silenced
Data from Hodgson, J. W., Argiropoulos, B., and
Brock, H. W. (2001). Site-specific recognition of
a 70-base-pair element containing d(GA)(n)
repeats mediates bithoraxoid polycomb group
response element-dependent silencing. Mol Cell
Biol 21, 4528-4543.
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Chromatin states can be inherited through meiosis
by the following generations
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Derepressed G1, G2, G3...
Repressed
Derepressed G0
GAL4 pulse in embryos
Re-cross red eyed flies
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