Hanna, C.W.* ; Taudt, A. ; Huang, J.* ; Gahurova, L.* ; Kranz, A.* ; Andrews, S.* ; Dean, W.* ; Stewart, A.F.* ; Colomé-Tatché, M. ; Kelsey, G.*
MLL2 conveys transcription-independent H3K4 trimethylation in oocytes.
Nat. Struct. Mol. Biol. 25, 73-82 (2018)
Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated with active promoters yet paradoxically occurs at untranscribed domains. Research to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The oocyte provides an attractive system to investigate these mechanisms, because extensive H3K4me3 acquisition occurs in nondividing cells. We developed low-input chromatin immunoprecipitation to interrogate H3K4me3, H3K27ac and H3K27me3 marks throughout oogenesis. In nongrowing oocytes, H3K4me3 was restricted to active promoters, but as oogenesis progressed, H3K4me3 accumulated in a transcription-independent manner and was targeted to intergenic regions, putative enhancers and silent H3K27me3-marked promoters. Ablation of the H3K4 methyltransferase gene Mll2 resulted in loss of transcription-independent H3K4 trimethylation but had limited effects on transcription-coupled H3K4 trimethylation or gene expression. Deletion of Dnmt3a and Dnmt3b showed that DNA methylation protects regions from acquiring H3K4me3. Our findings reveal two independent mechanisms of targeting H3K4me3 to genomic elements, with MLL2 recruited to unmethylated CpG-rich regions independently of transcription.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
Publication type
Article: Journal article
Document type
Scientific Article
Thesis type
Editors
Keywords
Embryonic Stem-cells; Dna Methylation; Chromatin-structure; Enhancer Function; Human Genome; Histone H3; Gene; Hematopoiesis; Initiation; Promoters
Keywords plus
Language
english
Publication Year
2018
Prepublished in Year
HGF-reported in Year
2018
ISSN (print) / ISBN
1545-9993
e-ISSN
1545-9985
ISBN
Book Volume Title
Conference Title
Conference Date
Conference Location
Proceedings Title
Quellenangaben
Volume: 25,
Issue: 1,
Pages: 73-82
Article Number: ,
Supplement: ,
Series
Publisher
Nature Publishing Group
Publishing Place
New York, NY
Day of Oral Examination
0000-00-00
Advisor
Referee
Examiner
Topic
University
University place
Faculty
Publication date
0000-00-00
Application date
0000-00-00
Patent owner
Further owners
Application country
Patent priority
Reviewing status
Peer reviewed
POF-Topic(s)
30205 - Bioengineering and Digital Health
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-554200-001
Grants
Copyright
Erfassungsdatum
2018-03-12