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Molecular and Cellular Biology, December 2008, p. 7323-7336, Vol. 28, No. 24
0270-7306/08/$08.00+0     doi:10.1128/MCB.00889-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Histone Modifications, but Not Nucleosomal Positioning, Correlate with Major Histocompatibility Complex Class I Promoter Activity in Different Tissues In Vivo{triangledown} ,{dagger}

Aparna S. Kotekar, Jocelyn D. Weissman, Anne Gegonne, Helit Cohen,{ddagger} and Dinah S. Singer*

Molecular Regulation Section, Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

Received 4 June 2008/ Returned for modification 8 July 2008/ Accepted 16 September 2008

To examine the role of chromatin in transcriptional regulation of the major histocompatibility complex (MHC) class I gene, we determined nucleosome occupancy and positioning, histone modifications, and H2A.Z occupancy across its regulatory region in murine tissues that have widely different expression levels. Surprisingly, nucleosome occupancy and positioning were indistinguishable between the spleen, kidney, and brain. In all three tissues, the 200 bp upstream of the transcription start site had low nucleosome occupancy. In contrast, nuclease hypersensitivity, histone modifications, and H2A.Z occupancy showed tissue-specific differences. Thus, tissue-specific differences in MHC class I transcription correlate with histone modifications and not nucleosomal organization. Further, activation of class I transcription by gamma interferon or its inhibition by {alpha}-amanitin did not alter nucleosome occupancy, positioning, nuclease hypersensitivity, histone modifications, or H2A.Z occupancy in any of the tissues examined. Thus, chromatin remodeling was not required to dynamically modulate transcriptional levels. These findings suggest that the MHC class I promoter remains poised and accessible to rapidly respond to infection and environmental cues.

* Corresponding author. Mailing address: Molecular Regulation Section, Experimental Immunology Branch, Bldg. 10, Rm. 4B-36, National Cancer Institute, NIH, Bethesda, MD 20892. Phone: (301) 496-9097. Fax: (301) 480-8449. E-mail: dinah.singer{at}nih.gov

{triangledown} Published ahead of print on 22 September 2008.

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

{ddagger} Present address: Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.

Molecular and Cellular Biology, December 2008, p. 7323-7336, Vol. 28, No. 24
0270-7306/08/$08.00+0     doi:10.1128/MCB.00889-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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