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CCAAT displacement protein/cut homolog recruits G9a histone lysine methyltransferase to repress transcription.

CCAAT displacement protein/cut homolog (CDP/cut) is a highly conserved homeodomain protein that contains three cut repeat sequences. CDP/cut is a transcriptional factor for many diverse cellular and viral genes that are involved in most cellular processes, including differentiation, development, and proliferation. Here, we report that CDP/cut interacts with a histone lysine methyltransferase (HKMT), G9a, in vivo and in vitro. The deletion of the cut repeats within CDP/cut abrogates the interaction with G9a. The transcriptional repressor function of CDP/cut is mediated through HKMT activity of G9a associated with CDP/cut. We show that the recruitment of G9a to the human p21(waf1/cdi1) promoter is contingent on the interaction with CDP/cut, and CDP/cut is directly associated with an increase in the methylation in vivo of Lys-9 in histone H3 within the CDP/cut-regulatory region of the p21(waf1/cdi1) promoter. The endogenous level of p21(waf1/cdi1) expression is repressed through CDP/cut and mediated by HKMT activity of G9a. Furthermore, we report the identification of G9a as a component of CDP/cut complex. G9a colocalizes with CDP/cut in the nucleus. These results indicate that G9a functions as a transcriptional corepressor in association with a CDP/cut complex. These studies now reveal the interaction of G9a with a sequence-specific transcription factor that regulates gene repression through CDP/cut.

Pubmed ID: 15269344

Authors

  • Nishio H
  • Walsh MJ

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

August 3, 2004

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL67099

Mesh Terms

  • Cell Nucleus
  • Cells, Cultured
  • Chromatin
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Histone-Lysine N-Methyltransferase
  • Homeodomain Proteins
  • Humans
  • In Vitro Techniques
  • Lysine
  • Nuclear Proteins
  • Promoter Regions, Genetic
  • Protein Methyltransferases
  • Repressor Proteins
  • Transcription, Genetic