TY - JOUR
T1 - Physical and Functional Association of a Trimethyl H3K4 Demethylase and Ring6a/MBLR, a Polycomb-like Protein
AU - Lee, Min Gyu
AU - Norman, Jessica
AU - Shilatifard, Ali
AU - Shiekhattar, Ramin
N1 - Funding Information:
We thank Drs. D. Reinberg, T. Jenuwein, and H. Koga for their antibodies; Dr. D. Bochar for recombinant AOF1; and Kazusa DNA Research Institute Foundation for KIAA0234 cDNA. We extend our gratitude to Drs. D. Baillat, C. Wynder, S. McMahon, and X. Zhang for helpful advice and technical assistance; to Henry Hoff for protein expression; and to Matt Hart, Tom Beer, Kaye Speicher, and Dr. D. Speicher for help with mass spectrometry. R.S. was supported by a grant from NIH RO1CA090758.
PY - 2007/3/9
Y1 - 2007/3/9
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2007.02.004
DO - 10.1016/j.cell.2007.02.004
M3 - Article
C2 - 17320162
AN - SCOPUS:33847383585
SN - 0092-8674
VL - 128
SP - 877
EP - 887
JO - Cell
JF - Cell
IS - 5
ER -