Physical and functional association of a trimethyl H3K4 demethylase and Ring6a/MBLR, a polycomb-like protein.

Article Details

Citation

Lee MG, Norman J, Shilatifard A, Shiekhattar R

Physical and functional association of a trimethyl H3K4 demethylase and Ring6a/MBLR, a polycomb-like protein.

Cell. 2007 Mar 9;128(5):877-87. Epub 2007 Feb 22.

PubMed ID
17320162 [ View in PubMed
]
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 C(5)HC(2) 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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Ascorbic acidLysine-specific demethylase 5DProteinHumans
Unknown
Cofactor
Details
Polypeptides
NameUniProt ID
Lysine-specific demethylase 5DQ9BY66Details