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Molecular and Cellular Biology, February 2008, p. 1171-1181, Vol. 28, No. 3
0270-7306/08/$08.00+0     doi:10.1128/MCB.01396-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Promoter Region-Specific Histone Incorporation by the Novel Histone Chaperone ANP32B and DNA-Binding Factor KLF5

Yoshiko Munemasa,^1, Toru Suzuki,^1,* Kenichi Aizawa,¹ Saku Miyamoto,¹ Yasushi Imai,¹ Takayoshi Matsumura,¹ Masami Horikoshi,² and Ryozo Nagai^1*

Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan,¹ Laboratory of Developmental Biology, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan²

Received 3 August 2007/ Returned for modification 3 September 2007/ Accepted 13 November 2007

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.

Published ahead of print on 26 November 2007.

These authors contributed equally.