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2016 ; 9
(1
): 60
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Genome-wide positioning of bivalent mononucleosomes
#MMPMID27634286
Sen S
; Block KF
; Pasini A
; Baylin SB
; Easwaran H
BMC Med Genomics
2016[Sep]; 9
(1
): 60
PMID27634286
show ga
BACKGROUND: Bivalent chromatin refers to overlapping regions containing
activating histone H3 Lys4 trimethylation (H3K4me3) and inactivating H3K27me3
marks. Existence of such bivalent marks on the same nucleosome has only recently
been suggested. Previous genome-wide efforts to characterize bivalent chromatin
have focused primarily on individual marks to define overlapping zones of
bivalency rather than mapping positions of truly bivalent mononucleosomes.
RESULTS: Here, we developed an efficacious sequential ChIP technique for
examining global positioning of individual bivalent nucleosomes. Using next
generation sequencing approaches we show that although individual H3K4me3 and
H3K27me3 marks overlap in broad zones, bivalent nucleosomes are focally enriched
in the vicinity of the transcription start site (TSS). These seem to occupy the
H2A.Z nucleosome positions previously described as salt-labile nucleosomes, and
are correlated with low gene expression. Although the enrichment profiles of
bivalent nucleosomes show a clear dependency on CpG island content, they
demonstrate a stark anti-correlation with methylation status. CONCLUSIONS: We
show that regional overlap of H3K4me3 and H3K27me3 chromatin tend to be upstream
to the TSS, while bivalent nucleosomes with both marks are mainly promoter
proximal near the TSS of CpG island-containing genes with poised/low expression.
We discuss the implications of the focal enrichment of bivalent nucleosomes
around the TSS on the poised chromatin state of promoters in stem cells.
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