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Mol Cell Proteomics. 2015 Jan;14(1):15-29. doi: 10.1074/mcp.M113.035089. Epub 2014 Oct 14.

Quantitative proteomics reveals a role for epigenetic reprogramming during human monocyte differentiation.

Author information

1
From the ‡Department of Biochemistry, Loma Linda University, Loma Linda, California 92354;
2
§Department of Pharmacology and Toxicology, UTMB at Galveston, Texas 77554;
3
¶Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore 117609.
4
From the ‡Department of Biochemistry, Loma Linda University, Loma Linda, California 92354; §Department of Pharmacology and Toxicology, UTMB at Galveston, Texas 77554; kazhang@utmb.edu.

Abstract

The differentiation of monocytes into macrophages and dendritic cells involves mechanisms for activation of the innate immune system in response to inflammatory stimuli, such as pathogen infection and environmental cues. Epigenetic reprogramming is thought to play an important role during monocyte differentiation. Complementary to cell surface markers, the characterization of monocytic cell lineages by mass spectrometry based protein/histone expression profiling opens a new avenue for studying immune cell differentiation. Here, we report the application of mass spectrometry and bioinformatics to identify changes in human monocytes during their differentiation into macrophages and dendritic cells. Our data show that linker histone H1 proteins are significantly down-regulated during monocyte differentiation. Although highly enriched H3K9-methyl/S10-phos/K14-acetyl tri-modification forms of histone H3 were identified in monocytes and macrophages, they were dramatically reduced in dendritic cells. In contrast, histone H4 K16 acetylation was found to be markedly higher in dendritic cells than in monocytes and macrophages. We also found that global hyperacetylation generated by the nonspecific histone deacetylase HDAC inhibitor Apicidin induces monocyte differentiation. Together, our data suggest that specific regulation of inter- and intra-histone modifications including H3 K9 methylation, H3 S10 phosphorylation, H3 K14 acetylation, and H4 K16 acetylation must occur in concert with chromatin remodeling by linker histones for cell cycle progression and differentiation of human myeloid cells into macrophages and dendritic cells.

PMID:
25316709
PMCID:
PMC4288251
DOI:
10.1074/mcp.M113.035089
[Indexed for MEDLINE]
Free PMC Article

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