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 |
| 巻 | 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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All Science Journal Classification (ASJC) codes
- Biochemistry
- Biophysics
- Molecular Biology
これを引用
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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. / Atsumi, Akihide; Tomita, Akihiro; Kiyoi, Hitoshi; Naoe, Tomoki.
：: Biochemical and Biophysical Research Communications, 巻 345, 番号 4, 14.07.2006, p. 1471-1480.研究成果: Article
TY - JOUR
T1 - 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
AU - Atsumi, Akihide
AU - Tomita, Akihiro
AU - Kiyoi, Hitoshi
AU - Naoe, Tomoki
PY - 2006/7/14
Y1 - 2006/7/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33744522801&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33744522801&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2006.05.047
DO - 10.1016/j.bbrc.2006.05.047
M3 - Article
C2 - 16730330
AN - SCOPUS:33744522801
VL - 345
SP - 1471
EP - 1480
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -