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Molecular and Cellular Biology, November 1999, p. 7816-7827, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

HDAC4, a Human Histone Deacetylase Related to Yeast HDA1, Is a Transcriptional Corepressor

Audrey H. Wang,1 Nicholas R. Bertos,1 Marko Vezmar,1 Nadine Pelletier,1 Milena Crosato,2 Henry H. Heng,3 John Th'ng,2 Jiahuai Han,4 and Xiang-Jiao Yang1,*

Molecular Oncology Group, Department of Medicine,1 and Lady Davis Institute for Medical Research,2 McGill University, Montreal, Quebec, and Biology Department, York University, North York, Ontario,3 Canada, and Department of Immunology, Scripps Research Institute, La Jolla, California4

Received 11 February 1999/Returned for modification 25 March 1999/Accepted 19 July 1999

Histone acetylation plays an important role in regulating chromatin structure and thus gene expression. Here we describe the functional characterization of HDAC4, a human histone deacetylase whose C-terminal part displays significant sequence similarity to the deacetylase domain of yeast HDA1. HDAC4 is expressed in various adult human tissues, and its gene is located at chromosome band 2q37. HDAC4 possesses histone deacetylase activity intrinsic to its C-terminal domain. When tethered to a promoter, HDAC4 represses transcription through two independent repression domains, with repression domain 1 consisting of the N-terminal 208 residues and repression domain 2 containing the deacetylase domain. Through a small region located at its N-terminal domain, HDAC4 interacts with the MADS-box transcription factor MEF2C. Furthermore, HDAC4 and MEF2C individually upregulate but together downmodulate c-jun promoter activity. These results suggest that HDAC4 interacts with transcription factors such as MEF2C to negatively regulate gene expression.

* Corresponding author. Mailing address: Molecular Oncology Group, Royal Victoria Hospital, Room H5-41, McGill University Health Centre, 687 Pine Ave. West, Montreal, QC H3A 1A1, Canada. Phone: (514) 842-1231, ext. 4490. Fax: (514) 843-1478. E-mail: yangxj{at}lan1.molonc.mcgill.ca.

Molecular and Cellular Biology, November 1999, p. 7816-7827, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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