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Molecular and Cellular Biology, April 2009, p. 1972-1986, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.01590-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Dynamic Histone Variant Exchange Accompanies Gene Induction in T Cells{triangledown} ,{dagger}

Elissa L. Sutcliffe,1 Ian A. Parish,1 Yi Qing He,1 Torsten Juelich,1 M. Louise Tierney,2 Danny Rangasamy,2 Peter J. Milburn,2 Christopher R. Parish,1 David J. Tremethick,2 and Sudha Rao1*

Division of Immunology and Genetics,1 Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia2

Received 10 October 2008/ Returned for modification 17 November 2008/ Accepted 19 December 2008

Changes in chromatin composition are often a prerequisite for gene induction. Nonallelic histone variants have recently emerged as key players in transcriptional control and chromatin modulation. While the changes in chromatin accessibility and histone posttranslational modification (PTM) distribution that accompany gene induction are well documented, the dynamics of histone variant exchange that parallel these events are still poorly defined. In this study, we have examined the changes in histone variant distribution that accompany activation of the inducible CD69 and heparanase genes in T cells. We demonstrate that the chromatin accessibility increases that accompany the induction of both of these genes are not associated with nucleosome loss but instead are paralleled by changes in histone variant distribution. Specifically, induction of these genes was paralleled by depletion of the H2A.Z histone variant and concomitant deposition of H3.3. Furthermore, H3.3 deposition was accompanied by changes in PTM patterns consistent with H3.3 enriching or depleting different PTMs upon incorporation into chromatin. Nevertheless, we present evidence that these H3.3-borne PTMs can be negated by recruited enzymatic activities. From these observations, we propose that H3.3 deposition may both facilitate chromatin accessibility increases by destabilizing nucleosomes and compete with recruited histone modifiers to alter PTM patterns upon gene induction.


* Corresponding author. Mailing address: Division of Immunology and Genetics, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia. Phone: 61-2-61250592. Fax: 61-2-61252595. E-mail: sudha.rao{at}anu.edu.au

{triangledown} Published ahead of print on 21 January 2009.

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


Molecular and Cellular Biology, April 2009, p. 1972-1986, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.01590-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




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