Mi-2 beta associates with BRG1 and RET finger protein at the distinct regions with transcriptional activating and repressing abilities.
Mi-2 beta is the main component of the nucleosome remodeling and deacetylase complex and plays an important role in epigenetic transcriptional repression. Here we show that the amino-terminal and carboxyl-terminal regions of Mi-2 beta have distinct transcriptional activities and bind to BRG1, a component of the SWI/SNF complex, and the RET finger protein (RFP), respectively. Analysis by luciferase reporter assay revealed that the amino-terminal region of Mi-2 beta has a strong transactivating ability, whereas its carboxyl-terminal region has transcriptional repressive activity. Co-localization and association of Mi-2, RFP, and histone deacetylase 1 suggested that these proteins cooperate in transcriptional repression. Furthermore, the functional importance of the association of Mi-2 beta and RFP was confirmed by using Rfp-/- fibroblasts. On the other hand, we demonstrated that Mi-2 and BRG1 were associated with each other and that the bromodomain region of BRG1 strongly suppressed transactivation by the amino-terminal region of Mi-2 beta. The findings that Mi-2 beta interacts with both transactivating and repressing proteins and directly associates with another chromatin remodeling protein, BRG1, provide new insight into the formation of multiprotein supercomplex involved in transcriptional regulation.
Shimono
Yohei
Y
Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Murakami
Hideki
H
Kawai
Kumi
K
Wade
Paul A
PA
Shimokata
Kaoru
K
Takahashi
Masahide
M
D000251:Adenosine Triphosphatases; D001324:Autoantigens / Q000378:metabolism* / Q000502:physiology; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection; D000070584:Tripartite Motif Proteins
D000251:Adenosine Triphosphatases; D001324:Autoantigens; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D009687:Nuclear Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C115323:CHD4 protein, human; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins; C084108:SMARCA4 protein, human