Title: CHROMATIN REMODELING: NEUROGENESIS
1CHROMATIN REMODELING NEUROGENESIS
The bromodomain of BRG1 recognizes acetylated
histone H4 lysine 8 (H4K8). BRG1 complex
repositions nucleosomes with respect to DNA,
allowing REST to form a more stable interaction
with DNA
N-terminus of REST interacts with mSin3 complex,
containing HDACs1 and 2. C-terminus of REST
interacts with the CoREST complex, containing
HDACs1 and 2, BRG1, the H3K4 demethylase LSD1 and
the H3K9 methylase G9a20. HDACs that are
recruited by mSin3 or CoREST remove acetyl groups
from H3 and H4 lysine residues. The removal of
acetylation from H3K9 stimulates LSD1 activity,
which removes di- and monomethylation marks from
H3K4 AND H3K9
Repressor element 1-silencing transcription-factor
(REST) recruited to target genes through its
zinc finger DNA binding domain with DNA is
stabilized by the ATP-dependent
chromatin-remodelling enzyme, BRG1
OOI AND WOOD, NATURE REV GENET, 2007
2CHROMATIN REMODELING NEUROGENESIS AND CANCER
HE
Removal of H3K9 acetylation by HDACs also
provides a substrate for G9a-mediated
methylation Thus, several modifications that are
associated with active gene transcription are
removed, and at least one mark that is associated
with gene repression is added
Methylated H3K9 can recruit the heterochromatic
protein HP1 through its chromodomain During
neuronal differentiation, REST is lost, allowing
target gene expression
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