Acetylation of histone H2B marks active enhancers and predicts CBP/p300 target genes
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Acetylation of histone H2B marks active enhancers and predicts CBP/p300 target genes. / Narita, Takeo; Higashijima, Yoshiki; Kilic, Sinan; Liebner, Tim; Walter, Jonas; Choudhary, Chunaram.
In: Nature Genetics, Vol. 55, 2023, p. 679-692.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Acetylation of histone H2B marks active enhancers and predicts CBP/p300 target genes
AU - Narita, Takeo
AU - Higashijima, Yoshiki
AU - Kilic, Sinan
AU - Liebner, Tim
AU - Walter, Jonas
AU - Choudhary, Chunaram
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - Chromatin features are widely used for genome-scale mapping of enhancers. However, discriminating active enhancers from other cis-regulatory elements, predicting enhancer strength and identifying their target genes is challenging. Here we establish histone H2B N-terminus multisite lysine acetylation (H2BNTac) as a signature of active enhancers. H2BNTac prominently marks candidate active enhancers and a subset of promoters and discriminates them from ubiquitously active promoters. Two mechanisms underlie the distinct H2BNTac specificity: (1) unlike H3K27ac, H2BNTac is specifically catalyzed by CBP/p300; (2) H2A–H2B, but not H3–H4, are rapidly exchanged through transcription-induced nucleosome remodeling. H2BNTac-positive candidate enhancers show a high validation rate in orthogonal enhancer activity assays and a vast majority of endogenously active enhancers are marked by H2BNTac and H3K27ac. Notably, H2BNTac intensity predicts enhancer strength and outperforms current state-of-the-art models in predicting CBP/p300 target genes. These findings have broad implications for generating fine-grained enhancer maps and modeling CBP/p300-dependent gene regulation.
AB - Chromatin features are widely used for genome-scale mapping of enhancers. However, discriminating active enhancers from other cis-regulatory elements, predicting enhancer strength and identifying their target genes is challenging. Here we establish histone H2B N-terminus multisite lysine acetylation (H2BNTac) as a signature of active enhancers. H2BNTac prominently marks candidate active enhancers and a subset of promoters and discriminates them from ubiquitously active promoters. Two mechanisms underlie the distinct H2BNTac specificity: (1) unlike H3K27ac, H2BNTac is specifically catalyzed by CBP/p300; (2) H2A–H2B, but not H3–H4, are rapidly exchanged through transcription-induced nucleosome remodeling. H2BNTac-positive candidate enhancers show a high validation rate in orthogonal enhancer activity assays and a vast majority of endogenously active enhancers are marked by H2BNTac and H3K27ac. Notably, H2BNTac intensity predicts enhancer strength and outperforms current state-of-the-art models in predicting CBP/p300 target genes. These findings have broad implications for generating fine-grained enhancer maps and modeling CBP/p300-dependent gene regulation.
U2 - 10.1038/s41588-023-01348-4
DO - 10.1038/s41588-023-01348-4
M3 - Journal article
C2 - 37024579
AN - SCOPUS:85152090956
VL - 55
SP - 679
EP - 692
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
ER -
ID: 344431225