Promoter region-specific histone incorporation by the novel histone chaperone ANP32B and DNA-binding factor KLF5.
Regulation of chromatin in eukaryotic transcription requires histone-modifying enzymes, nucleosome remodeling complexes, and histone chaperones. Specific regulation of histone incorporation/eviction by histone chaperones on the promoter (e.g., region specific) is still poorly understood. In the present study, we show that direct and functional interaction of histone chaperone and DNA-binding transcription factor leads to promoter region-specific histone incorporation and inhibition of histone acetylation. We report here that the DNA-binding transcription factor Krüppel-like factor 5 (KLF5) interacts with the novel histone chaperone acidic nuclear phosphoprotein 32B (ANP32B), leading to transcriptional repression of a KLF5-downstream gene. We further show that recruitment of ANP32B onto the promoter region requires KLF5 and results in promoter region-specific histone incorporation and inhibition of histone acetylation by ANP32B. Extracellular stimulus (e.g., phorbol ester) regulates this mechanism in the cell. Collectively, we have identified a novel histone chaperone, ANP32B, and through analysis of the actions of this factor show a new mechanism of promoter region-specific transcriptional regulation at the chromatin level as mediated by the functional interaction between histone chaperone and DNA-binding transcription factor.
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Yoshiko
Y
Munemasa
Toru
T
Suzuki
Kenichi
K
Aizawa
Saku
S
Miyamoto
Yasushi
Y
Imai
Takayoshi
T
Matsumura
Masami
M
Horikoshi
Ryozo
R
Nagai
D000107:Acetylation; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D018832:Molecular Chaperones / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
C490341:ANP32B protein, human; D004268:DNA-Binding Proteins; D006657:Histones; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D018832:Molecular Chaperones; D009687:Nuclear Proteins