Acetylation of histone H2B marks active enhancers and predicts CBP/p300 target genes

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 acetylatio...

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Veröffentlicht in:Nature genetics 2023-04, Vol.55 (4), p.679-692
Hauptverfasser: Narita, Takeo, Higashijima, Yoshiki, Kilic, Sinan, Liebner, Tim, Walter, Jonas, Choudhary, Chunaram
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container_title Nature genetics
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creator Narita, Takeo
Higashijima, Yoshiki
Kilic, Sinan
Liebner, Tim
Walter, Jonas
Choudhary, Chunaram
description 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. Histone H2B N-terminus multisite lysine acetylation (H2BNTac) is identified as a signature of active enhancers. H2BNTac-positive putative enhancers are validated using orthogonal enhancer activity assays.
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subjects 45
45/15
631/208/177
631/208/200
Acetylation
Agriculture
Animal Genetics and Genomics
Antibodies
Biomedical and Life Sciences
Biomedicine
Cancer Research
Chromatin
Enhancer Elements, Genetic - genetics
Enhancers
Gene Expression Regulation
Gene Function
Gene mapping
Gene regulation
Genes
Genomes
Histone H2B
Histones
Histones - genetics
Histones - metabolism
Human Genetics
Lysine
N-Terminus
Promoters
Regulatory sequences
Stem cells
title Acetylation of histone H2B marks active enhancers and predicts CBP/p300 target genes
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