Linked Life Data

21502505

Source:http://linkedlifedata.com/resource/pubmed/id/21502505

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2011-5-4
pubmed:abstractText
It is well-documented that the methylation of histone H3 lysine 4 (H3K4) and of H3K9 are mutually exclusive, an epigenetic phenomenon conserved from yeast to humans. How this opposed methylation modification is accomplished and coordinated in mammalian cells is poorly understood. Here we report that the H3K9 trimethyl demethylase JMJD2B is an integral component of the H3K4-specific methyltransferase, the mixed-lineage leukemia (MLL) 2 complex. We show that the JMJD2B/MLL2 complex is copurified with estrogen receptor ? (ER?) and is required for ER?-regulated transcription. We demonstrate that H3K9 demethylation and H3K4 methylation are coordinated in ER?-activated transcription such that H3K9 demethylation is a prerequisite for H3K4 methylation. Significantly, depletion of JMJD2B impairs the estrogen-induced G(1)/S transition of the cell cycle in vitro and inhibits breast tumorigenesis in vivo. Interestingly, JMJD2B itself is an ER? target gene, and forms a feed-forward regulatory loop in regulation of the hormone response. Our results provide a molecular basis for the coordinated H3K4 methylation/H3K9 demethylation in transcription activation, link the trimethyl demethylase JMJD2B to euchromatin functions, and provide a mechanism for JMJD2B in breast carcinogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7541-6
pubmed:dateRevised
2011-11-3
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Histone demethylase JMJD2B coordinates H3K4/H3K9 methylation and promotes hormonally responsive breast carcinogenesis.
pubmed:affiliation
Key Laboratory of Carcinogenesis and Translational Research Ministry of Education, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't