H3K4/H3K9me3 Bivalent Chromatin Domains Targeted by Lineage-Specific DNA Methylation Pauses Adipocyte Differentiation

Autor: Matsumura, Y., Nakaki, R., Inagaki, T., Yoshida, A., Kano, Y., Kimura, Hiroshi, Tanaka, T., Tsutsumi, S., Nakao, M., Doi, T., Fukami, K., Osborne, T. F., Kodama, T., Aburatani, H., Sakai, J.
Rok vydání: 2015
Předmět:
Histones/chemistry/*genetics
H3K27me3
Cellular differentiation
epigenome
DNA Methylation
lineage commitment
bivalent chromatin domains
environment and public health
Histone methylation
H3K9me3
adipogenesis
Histones
Chromatin/metabolism
Mice
CEBPA
Adipocytes
Adipocytes/*cytology/physiology
Animals
Cell Lineage
Molecular Biology
Transcription factor
Cells
Cultured
Histone-Lysine N-Methyltransferase/metabolism
DNA methylation
biology
Mesenchymal Stem Cells
Cell Differentiation
Histone-Lysine N-Methyltransferase
3T3 Cells
H3K4me3
Cell Biology
PPAR gamma/*metabolism
gene-body methylation
Molecular biology
Chromatin
CCAAT-Enhancer-Binding Proteins/*metabolism
Protein Structure
Tertiary
PPAR gamma
Histone
CCAAT-Enhancer-Binding Proteins
biology.protein
RNA polymerase II
Mesenchymal Stromal Cells/cytology/physiology
Bivalent chromatin
Zdroj: Molecular Cell. 60:584-596
ISSN: 1097-2765
DOI: 10.1016/j.molcel.2015.10.025
Popis: 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.
Databáze: OpenAIRE
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