@article{2a1414abcdaa40eb86c0a06ae42ff8f9,
title = "H3K4/H3K9me3 Bivalent Chromatin Domains Targeted by Lineage-Specific DNA Methylation Pauses Adipocyte Differentiation",
abstract = "Bivalent H3K4me3 and H3K27me3 chromatin domains in embryonic stem cells keep active developmental regulatory genes expressed at very low levels and poised for activation. Here, we show an alternative and previously unknown bivalent modified histone signature in lineage-committed mesenchymal stem cells and preadipocytes that pairs H3K4me3 with H3K9me3 to maintain adipogenic master regulatory genes (Cebpa and Pparg) expressed at low levels yet poised for activation when differentiation is required. We show lineage-specific gene-body DNA methylation recruits H3K9 methyltransferase SETDB1, which methylates H3K9 immediately downstream of transcription start sites marked with H3K4me3 to establish the bivalent domain. At the Cebpa locus, this prevents transcription factor C/EBPβ binding, histone acetylation, and further H3K4me3 deposition and is associated with pausing of RNA polymerase II, which limits Cebpa gene expression and adipogenesis.",
keywords = "Adipogenesis, Bivalent chromatin domains, DNA methylation, Epigenome, Gene-body methylation, H3K27me3, H3K4me3, H3K9me3, Histone methylation, Lineage commitment, RNA polymerase II",
author = "Yoshihiro Matsumura and Ryo Nakaki and Takeshi Inagaki and Ayano Yoshida and Yuka Kano and Hiroshi Kimura and Toshiya Tanaka and Shuichi Tsutsumi and Mitsuyoshi Nakao and Takefumi Doi and Kiyoko Fukami and Osborne, {Timothy F.} and Tatsuhiko Kodama and Hiroyuki Aburatani and Juro Sakai",
note = "Funding Information: We thank Aoi Uchida, Saki Kawashima, Atena Nishikawa, Akashi Taguchi-Izumi, and Kaori Shiina for technical assistance; Hifumi Tsuboi for secretary assistance; Dr. Ken-ichi Wakabayashi for some of ChIP-seq data; Dr. Shogo Yamamoto for submission of ChIP-seq data; Dr. Yoichi Shinkai for SETDB1 conditional knockout ESCs; Dr. Shoji Tajima for expression plasmids for MBD domain of MBD1; Dr. Toshio Kitamura for pMXs-puro plasmid; and other members of the Sakai laboratory for helpful discussions. This study was supported by grants-in-aid for young scientists (to Y.M. and T.I.), for scientific research (to J.S. and T.I.), and for scientific research on innovative areas (to J. S. and T. I.), and Translational Systems Biology and Medicine Initiative (TSBMI) from the Ministry of Education, Science, Sports and Culture (MEXT), Japan. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = nov,
day = "19",
doi = "10.1016/j.molcel.2015.10.025",
language = "English",
volume = "60",
pages = "584--596",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "4",
}