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2017 ; 6
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A high-resolution map of transcriptional repression
#MMPMID28318487
Liang Z
; Brown KE
; Carroll T
; Taylor B
; Vidal IF
; Hendrich B
; Rueda D
; Fisher AG
; Merkenschlager M
Elife
2017[Mar]; 6
(ä): ä PMID28318487
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Turning genes on and off is essential for development and homeostasis, yet little
is known about the sequence and causal role of chromatin state changes during the
repression of active genes. This is surprising, as defective gene silencing
underlies developmental abnormalities and disease. Here we delineate the sequence
and functional contribution of transcriptional repression mechanisms at high
temporal resolution. Inducible entry of the NuRD-interacting transcriptional
regulator Ikaros into mouse pre-B cell nuclei triggered immediate binding to
target gene promoters. Rapid RNAP2 eviction, transcriptional shutdown, nucleosome
invasion, and reduced transcriptional activator binding required chromatin
remodeling by NuRD-associated Mi2beta/CHD4, but were independent of HDAC
activity. Histone deacetylation occurred after transcriptional repression.
Nevertheless, HDAC activity contributed to stable gene silencing. Hence, high
resolution mapping of transcriptional repression reveals complex and
interdependent mechanisms that underpin rapid transitions between transcriptional
states, and elucidates the temporal order, functional role and mechanistic
separation of NuRD-associated enzymatic activities.
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