Physical and Functional Association of a Trimethyl H3K4 Demethylase and Ring6a/MBLR, a Polycomb-like Protein

Min Gyu Lee, Jessica Norman, Ali Shilatifard, Ramin Shiekhattar

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

Histone methylation is a posttranslational modification regulating chromatin structure and gene regulation. BHC110/LSD1 was the first histone demethylase described to reverse dimethyl histone H3 lysine 4 (H3K4). Here we show that JARID1d, a JmjC-domain-containing protein, specifically demethylates trimethyl H3K4. Detailed mapping analysis revealed that besides the JmjC domain, the BRIGHT and zinc-finger-like C5HC2 domains are required for maximum catalytic activity. Importantly, isolation of native JARID1d complexes from human cells revealed the association of the demethylase with a polycomb-like protein Ring6a/MBLR. Ring6a/MBLR not only directly interacts with JARID1d but also regulates its enzymatic activity. We show that JARID1d and Ring6a occupy human Engrailed 2 gene and regulate its expression and H3K4 methylation levels. Depletion of JARID1d enhanced recruitment of the chromatin remodeling complex, NURF, and the basal transcription machinery near the transcriptional start site, revealing a role for JARID1d in regulation of transcriptional initiation through H3K4 demethylation.

Original languageEnglish (US)
Pages (from-to)877-887
Number of pages11
JournalCell
Volume128
Issue number5
DOIs
StatePublished - Mar 9 2007
Externally publishedYes

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Methylation
Histones
Chromatin
Histone Demethylases
Chromatin Assembly and Disassembly
Zinc Fingers
Transcription
Post Translational Protein Processing
Gene expression
Genes
Lysine
Machinery
Zinc
Catalyst activity
Proteins
Cells
Association reactions
Protein Domains

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Physical and Functional Association of a Trimethyl H3K4 Demethylase and Ring6a/MBLR, a Polycomb-like Protein. / Lee, Min Gyu; Norman, Jessica; Shilatifard, Ali; Shiekhattar, Ramin.

In: Cell, Vol. 128, No. 5, 09.03.2007, p. 877-887.

Research output: Contribution to journalArticle

Lee, Min Gyu ; Norman, Jessica ; Shilatifard, Ali ; Shiekhattar, Ramin. / Physical and Functional Association of a Trimethyl H3K4 Demethylase and Ring6a/MBLR, a Polycomb-like Protein. In: Cell. 2007 ; Vol. 128, No. 5. pp. 877-887.
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