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Histone Methylation Patterns Are Cell-Type Specific in Human Monocytes and Lymphocytes and Well Maintained at Core Genes¹

Feng Miao^*, Xiwei Wu, Lingxiao Zhang^*, Arthur D. Riggs and Rama Natarajan^2,*

^* Department of Diabetes, Department of Biomedical Informatics, and Department of Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010

Different immune cells are expected to have unique, obligatory, and stable epigenomes for cell-specific functions. Histone methylation is recognized as a major layer of the cellular epigenome. However, the discovery of histone demethylases raises questions about the stability of histone methylation and its role in the epigenome. In this study, we used chromatin-immunoprecipitation combined with microarrays to map histone H3K9 dimethylation (H3K9Me2) patterns in gene coding and CpG island regions in human primary monocytes and lymphocytes. This chromosomal mark showed consistent distribution patterns in either monocytes or lymphocytes from multiple volunteers despite age or gender, but the pattern in monocytes was clearly distinct from lymphocytes of the same population. Gene Set Enrichment analysis, a bioinformatics tool, revealed that H3K9Me2 candidate genes are enriched in many tightly controlled signaling and cell-type specific pathways. These results demonstrate that monocytes and lymphocytes have distinct epigenomes and H3K9Me2 may play regulatory roles in the transcription of genes indispensable for maintaining immune responses and cell-type specificity.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the National Institutes of Health (R01 DK065073) and the Juvenile Diabetes Research Foundation International (to R.N.) and in part by a General Clinical Research Center grant from the National Center for Research Resources (M01RR00043 to City of Hope).

² Address correspondence and reprint requests to Dr. Rama Natarajan, Department of Diabetes, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010. E-mail address: RNatarajan{at}coh.org

³ Abbreviations used in this paper: PTM, post translational modification; H3K9Me2, H3 lysine-9 dimethylation; ChIP-chip, chromatin immunoprecipitation coupled to DNA microarray analysis; GSEA, gene set enrichment analysis; ES, enrichment score; FDR, false discovery rate.

⁴ The online version of this article contains supplemental material.

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