BMC Genomics | |
Defining super-enhancers by highly ranked histone H4 multi-acetylation levels identifies transcription factors associated with glioblastoma stem-like properties | |
Research | |
Atsushi Natsume1  Keisuke Katsushima2  Yutaka Kondo2  Bogumil Kaczkowski3  S. Thomas Kelly4  Jen-Chien Chang4  Aki Minoda5  Hisami Watanabe6  Nando D. Das6  Takashi Umehara7  Marina Lizio8  Chung-Chau Hon8  Shinsuke Ito9  Haruhiko Koseki1,10  | |
[1] Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan;Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan;Laboratory for Applied Regulatory Genomics Network Analysis, RIKEN IMS, Yokohama, Japan;Laboratory for Cellular Epigenomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan;Laboratory for Cellular Epigenomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan;Department of Cell Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, Netherlands;Laboratory for Epigenetics Drug Discovery, RIKEN Center for Biosystems Dynamics Research, Yokohama, Japan;Laboratory for Epigenetics Drug Discovery, RIKEN Center for Biosystems Dynamics Research, Yokohama, Japan;PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan;Laboratory for Genome Information Analysis, RIKEN IMS, Yokohama, Japan;Laboratory of Developmental Genetics, RIKEN IMS, Yokohama, Japan;Laboratory of Developmental Genetics, RIKEN IMS, Yokohama, Japan;Immune Regulation, Advanced Research Departments, Graduate School of Medicine, Chiba University, Chiba, Japan; | |
关键词: Epigenetics; Histone acetylation; Inhibitor; Nucleosome; Tumorigenesis; | |
DOI : 10.1186/s12864-023-09659-w | |
received in 2023-07-26, accepted in 2023-09-07, 发布年份 2023 | |
来源: Springer | |
【 摘 要 】
BackgroundSuper-enhancers (SEs), which activate genes involved in cell-type specificity, have mainly been defined as genomic regions with top-ranked enrichment(s) of histone H3 with acetylated K27 (H3K27ac) and/or transcription coactivator(s) including a bromodomain and extra-terminal domain (BET) family protein, BRD4. However, BRD4 preferentially binds to multi-acetylated histone H4, typically with acetylated K5 and K8 (H4K5acK8ac), leading us to hypothesize that SEs should be defined by high H4K5acK8ac enrichment at least as well as by that of H3K27ac.ResultsHere, we conducted genome-wide profiling of H4K5acK8ac and H3K27ac, BRD4 binding, and the transcriptome by using a BET inhibitor, JQ1, in three human glial cell lines. When SEs were defined as having the top ranks for H4K5acK8ac or H3K27ac signal, 43% of H4K5acK8ac-ranked SEs were distinct from H3K27ac-ranked SEs in a glioblastoma stem-like cell (GSC) line. CRISPR-Cas9–mediated deletion of the H4K5acK8ac-preferred SEs associated with MYCN and NFIC decreased the stem-like properties in GSCs.ConclusionsCollectively, our data highlights H4K5acK8ac’s utility for identifying genes regulating cell-type specificity.
【 授权许可】
CC BY
© BioMed Central Ltd., part of Springer Nature 2023
【 预 览 】
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