Histone deacetylase 3 (HDAC3) is recruited to target promoters by PML-RARα as a component of the N-CoR co-repressor complex to repress transcription in vivo

Akihide Atsumi, Akihiro Tomita, Hitoshi Kiyoi, Tomoki Naoe

研究成果: Article

34 引用 (Scopus)

抄録

PML-RARα is a chimeric transcription factor tightly associated with acute promyelocytic leukemia. PML-RARα plays an important role in the aberrant transcription repression on the target genes of wild-type retinoic acid receptors. Here, we demonstrated that HDAC3, one component of the N-CoR transcription repressor complex, is a key regulator of the transcription repression by PML-RARα in vivo. Using immunoprecipitation, we demonstrated that PML-RARα interacts with N-CoR/HDAC3 in vivo without ligand. Next, using chromatin immunoprecipitation (ChIP) assay, this N-CoR/HDAC3 co-repressor complex was recruited to the endogenous target promoters (RARβ and CYP26) through PML-RARα. The neighboring histones were de-acetylated and gene expression was repressed. When HDAC3 protein was knocked down by RNA interference in PML-RARα-expressing cells, the endogenous target genes were significantly activated, which was also confirmed by promoter-luciferase reporter assay. These results provide evidence to show that the N-CoR/HDAC3 co-repressor complex is involved in the aberrant transcription regulation in PML-RARα-expressing cells.

元の言語English
ページ(範囲)1471-1480
ページ数10
ジャーナルBiochemical and Biophysical Research Communications
345
発行部数4
DOI
出版物ステータスPublished - 14-07-2006
外部発表Yes

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Co-Repressor Proteins
Transcription
Assays
Genes
Acute Promyelocytic Leukemia
Retinoic Acid Receptors
Chromatin Immunoprecipitation
RNA Interference
Luciferases
Immunoprecipitation
Gene expression
Histones
Chromatin
Transcription Factors
histone deacetylase 3
RNA
Ligands
Gene Expression
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Biophysics
  • Molecular Biology

これを引用

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abstract = "PML-RARα is a chimeric transcription factor tightly associated with acute promyelocytic leukemia. PML-RARα plays an important role in the aberrant transcription repression on the target genes of wild-type retinoic acid receptors. Here, we demonstrated that HDAC3, one component of the N-CoR transcription repressor complex, is a key regulator of the transcription repression by PML-RARα in vivo. Using immunoprecipitation, we demonstrated that PML-RARα interacts with N-CoR/HDAC3 in vivo without ligand. Next, using chromatin immunoprecipitation (ChIP) assay, this N-CoR/HDAC3 co-repressor complex was recruited to the endogenous target promoters (RARβ and CYP26) through PML-RARα. The neighboring histones were de-acetylated and gene expression was repressed. When HDAC3 protein was knocked down by RNA interference in PML-RARα-expressing cells, the endogenous target genes were significantly activated, which was also confirmed by promoter-luciferase reporter assay. These results provide evidence to show that the N-CoR/HDAC3 co-repressor complex is involved in the aberrant transcription regulation in PML-RARα-expressing cells.",
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AU - Kiyoi, Hitoshi

AU - Naoe, Tomoki

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