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Molecular and Cellular Biology, June 2005, p. 4650-4661, Vol. 25, No. 11
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.11.4650-4661.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mapping Global Histone Methylation Patterns in the Coding Regions of Human Genes{dagger}

Feng Miao and Rama Natarajan*

Gonda Diabetes Center, Beckman Research Institute of City of Hope, Duarte, California

Received 5 October 2004/ Returned for modification 8 November 2004/ Accepted 1 March 2005

Histone methylation patterns in the human genome, especially in euchromatin regions, have not been systematically characterized. In this study, we examined the profile of histone H3 methylation (Me) patterns at different lysines (Ks) in the coding regions of human genes by genome-wide location analyses by using chromatin immunoprecipitation linked to cDNA arrays. Specifically, we compared H3-KMe marks known to be associated with active gene expression, namely, H3-K4Me, H3-K36Me, and H3-K79Me, as well as those associated with gene repression, namely, H3-K9Me, H3-K27Me, and H4-K20Me. We further compared these to histone lysine acetylation (H3-K9/14Ac). Our results demonstrated that: first, close correlations are present between active histone marks except between H3-K36Me2 and H3-K4Me2. Notably, histone H3-K79Me2 is closely associated with H3-K4Me2 and H3-K36Me2 in the coding regions. Second, close correlations are present between histone marks associated with gene silencing such as H3-K9Me3, H3-K27Me2, and H4-K20Me2. Third, a poor correlation is observed between euchromatin marks (H3-K9/K14Ac, H3-K4Me2, H3-K36Me2, and H3-K79Me2) and heterochromatin marks (H3-K9Me2, H3-K9Me3, H3-K27Me2, and H4-K20Me2). Fourth, H3-K9Me2 is neither associated with active nor repressive histone methylations. Finally, histone H3-K4Me2, H3-K4Me3, H3-K36Me2, and H3-K79Me2 are associated with hyperacetylation and active genes, whereas H3-K9Me2, H3-K9Me3, H3-K27Me2, and H4-K20Me2 are associated with hypoacetylation. These data provide novel new information regarding histone KMe distribution patterns in the coding regions of human genes.

* Corresponding author. Mailing address: Gonda Diabetes Center, Beckman Research Institute of the City of Hope, 1500 East Duarte Rd., Duarte, CA 91010. Phone: (626) 359-8111, ext. 62289. Fax: (626) 301-8136. E-mail: rnatarajan{at}coh.org.

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

Molecular and Cellular Biology, June 2005, p. 4650-4661, Vol. 25, No. 11
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.11.4650-4661.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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