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Molecular and Cellular Biology, November 2006, p. 8303-8315, Vol. 26, No. 22
0270-7306/06/$08.00+0     doi:10.1128/MCB.00887-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Transcriptional Coactivator PC4, a Chromatin-Associated Protein, Induces Chromatin Condensation{triangledown} ,{dagger}

Chandrima Das,1,{ddagger} Kohji Hizume,2,{ddagger} Kiran Batta,1 B. R. Prashanth Kumar,1 Shrikanth S. Gadad,1 Semanti Ganguly,3 Stephanie Lorain,4 Alain Verreault,4 Parag P. Sadhale,3 Kunio Takeyasu,2 and Tapas K. Kundu1*

Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India,1 Laboratory of Plasma Membrane and Nuclear Signaling, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan,2 Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India,3 Chromosome Dynamics Laboratory, Cancer Research, Clare Hall Laboratories, Blanche Lane, South Mimms, United Kingdom4

Received 18 May 2006/ Returned for modification 30 June 2006/ Accepted 10 August 2006

Human transcriptional coactivator PC4 is a highly abundant multifunctional protein which plays diverse important roles in cellular processes, including transcription, replication, and repair. It is also a unique activator of p53 function. Here we report that PC4 is a bona fide component of chromatin with distinct chromatin organization ability. PC4 is predominantly associated with the chromatin throughout the stages of cell cycle and is broadly distributed on the mitotic chromosome arms in a punctate manner except for the centromere. It selectively interacts with core histones H3 and H2B; this interaction is essential for PC4-mediated chromatin condensation, as demonstrated by micrococcal nuclease (MNase) accessibility assays, circular dichroism spectroscopy, and atomic force microscopy (AFM). The AFM images show that PC4 compacts the 100-kb reconstituted chromatin distinctly compared to the results seen with the linker histone H1. Silencing of PC4 expression in HeLa cells results in chromatin decompaction, as evidenced by the increase in MNase accessibility. Knocking down of PC4 up-regulates several genes, leading to the G2/M checkpoint arrest of cell cycle, which suggests its physiological role as a chromatin-compacting protein. These results establish PC4 as a new member of chromatin-associated protein family, which plays an important role in chromatin organization.

* Corresponding author. Mailing address: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India. Phone: (0091) 80-2208-2841. Fax: (0091) 80-2208-2766. E-mail: tapas{at}jncasr.ac.in.

{triangledown} Published ahead of print on 18 September 2006.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} C.D. and K.H. contributed equally.

Molecular and Cellular Biology, November 2006, p. 8303-8315, Vol. 26, No. 22
0270-7306/06/$08.00+0     doi:10.1128/MCB.00887-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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