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Molecular and Cellular Biology, February 2008, p. 967-976, Vol. 28, No. 3
0270-7306/08/$08.00+0     doi:10.1128/MCB.01020-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Brd4 Recruits P-TEFb to Chromosomes at Late Mitosis To Promote G1 Gene Expression and Cell Cycle Progression{triangledown}

Zhiyuan Yang, Nanhai He, and Qiang Zhou*

Department of Molecular and Cell Biology, University of California, Berkeley, California 94720

Received 10 June 2007/ Returned for modification 11 September 2007/ Accepted 9 November 2007

Brd4, a bromodomain protein capable of interacting with acetylated histones, is implicated in transmitting epigenetic memory through mitosis. It also functions as an associated factor and positive regulator of P-TEFb, a Cdk9-cyclin T1 heterodimer that stimulates transcriptional elongation by phosphorylating RNA polymerase II. In the present study, experiments were performed to determine whether these two functions of Brd4 are interrelated and, if so, how they may impact cell cycle progression. Our data demonstrate that while the P-TEFb level remains constant, the Brd4-P-TEFb interaction increases dramatically in cells progressing from late mitosis to early G1. Concurrently, P-TEFb is recruited to chromosomes, beginning around mid- to late anaphase and before nuclear envelope/lamina formation and nuclear import of other general transcription factors. Importantly, the recruitment of P-TEFb depends on Brd4. Abrogation of this process through Brd4 knockdown reduces the binding of P-TEFb to and expression of key G1 and growth-associated genes, leading to G1 cell cycle arrest and apoptosis. Because P-TEFb is synonymous with productive elongation, its recruitment by Brd4 to chromosomes at late mitosis may indicate those genes whose active transcription status must be preserved across cell division.

* Corresponding author. Mailing address: Department of Molecular and Cell Biology, University of California, 622 Barker Hall, Room 3202, Berkeley, CA 94720. Phone: (510) 643-0494. Fax: (510) 643-6334. E-mail: qzhou{at}berkeley.edu

{triangledown} Published ahead of print on 26 November 2007.

Molecular and Cellular Biology, February 2008, p. 967-976, Vol. 28, No. 3
0270-7306/08/$08.00+0     doi:10.1128/MCB.01020-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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