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
N1 - Funding Information:
We thank Dr. Shi Y.B. and Dr. Buchholz D.R. in NICHD/NIH for critical reading. We also thank Ms. Kira, Ms. Yamaji, Mr. Ninomiya, Mr. Koyama and Mr. Nakano for helping our lab work. This work is supported by Grants-in-Aid from the Scientific Research of Education, Culture, Sports, Science and Technology, Japan, and the Public Trust Haraguchi Memorial Cancer Research Fund, Japan.
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.
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U2 - 10.1016/j.bbrc.2006.05.047
DO - 10.1016/j.bbrc.2006.05.047
M3 - Article
C2 - 16730330
AN - SCOPUS:33744522801
SN - 0006-291X
VL - 345
SP - 1471
EP - 1480
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -