NDLI: Defining super-enhancers by highly ranked histone H4 multi-acetylation levels identifies transcription factors associated with glioblastoma stem-like properties

Content Provider	Springer Nature : BioMed Central
Author	Das, Nando D. Chang, Jen-Chien Hon, Chung-Chau Kelly, S. Thomas Ito, Shinsuke Lizio, Marina Kaczkowski, Bogumil Watanabe, Hisami Katsushima, Keisuke Natsume, Atsushi Koseki, Haruhiko Kondo, Yutaka Minoda, Aki Umehara, Takashi
Abstract	Background Super-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. Results Here, 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. Conclusions Collectively, our data highlights H4K5acK8ac’s utility for identifying genes regulating cell-type specificity.
Related Links	https://bmcgenomics.biomedcentral.com/counter/pdf/10.1186/s12864-023-09659-w.pdf
Ending Page	19
Page Count	19
Starting Page	1
File Format	HTM / HTML
ISSN	14712164
DOI	10.1186/s12864-023-09659-w
Journal	BMC Genomics
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2023-09-27
Access Restriction	Open
Subject Keyword	Life Sciences Microarrays Proteomics Animal Genetics and Genomics Microbial Genetics and Genomics Plant Genetics and Genomics Epigenetics Histone acetylation Inhibitor Nucleosome Tumorigenesis
Content Type	Text
Resource Type	Article
Subject	Biotechnology Genetics
Journal Impact Factor	3.5/2023
5-Year Journal Impact Factor	4.1/2023

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