Article

H4K20 METHYLATION REGULATES QUIESCENCE AND CHROMATIN COMPACTION.

Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA. Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA. Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles and Department of Biological Chemistry, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Molecular biology of the cell (Impact Factor: 5.98). 08/2013; DOI: 10.1091/mbc.E12-07-0529
Source: PubMed

ABSTRACT The transition between proliferation and quiescence is frequently associated with changes in gene expression, in the extent of chromatin compaction and in histone modifications, but whether changes in chromatin state actually regulate cell cycle exit with quiescence is unclear. We discovered that primary human fibroblasts induced into quiescence exhibited tighter chromatin compaction. Mass spectrometry analysis of histone modifications revealed that H4K20me2 and -me3 are increased in quiescence and that other histone modifications are present at similar levels in proliferating and quiescent cells. Analysis of cells in S, G2/M, and G1 phases shows that H4K20me1 increases after S phase and is converted to -me2 and -me3 in quiescence. Knockdown of the enzymes that create H4K20me2 and -me3 resulted in an increased fraction of cells in S phase, a defect in exiting the cell cycle, and decreased chromatin compaction. Overexpression of Suv4-20h1, the enzyme that creates H4K20me2 from H4K20me1, resulted in G2 arrest, consistent with a role for H4K20me1 in mitosis. The results suggest that the same lysine on H4K20 may, in its different methylation states, facilitate mitotic functions in M phase and promote chromatin compaction and cell cycle exit in quiescent cells.

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