title: Physical and functional association of a trimethyl H3K4 demethylase and Ring6a/MBLR, a polycomb-like protein.
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.
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Min Gyu
authors.initials: MG
authors.lastname: Lee
authors.forename: Jessica
authors.initials: J
authors.lastname: Norman
authors.forename: Ali
authors.initials: A
authors.lastname: Shilatifard
authors.forename: Ramin
authors.initials: R
authors.lastname: Shiekhattar
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D056466:Histone Demethylases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008745:Methylation; D015778:Minor Histocompatibility Antigens; D009419:Nerve Tissue Proteins / Q000235:genetics; D063150:Polycomb Repressive Complex 1; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification; D012097:Repressor Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D016335:Zinc Fingers; D000099266:Engrailed 2 Protein
chemical_list: D056466:Histone Demethylases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; D018398:Homeodomain Proteins; D015778:Minor Histocompatibility Antigens; D009419:Nerve Tissue Proteins; D063150:Polycomb Repressive Complex 1; D011506:Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D000099266:Engrailed 2 Protein; C472312:PCGF6 protein, human; C095561:KDM5D protein, human