H4K20 methylation regulates quiescence and chromatin compaction.
The transition between proliferation and quiescence is frequently associated with changes in gene expression, extent of chromatin compaction, and histone modifications, but whether changes in chromatin state actually regulate cell cycle exit with quiescence is unclear. We find that primary human fibroblasts induced into quiescence exhibit tighter chromatin compaction. Mass spectrometry analysis of histone modifications reveals that H4K20me2 and H4K20me3 increase in quiescence and 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 H4K20me2 and H4K20me3 in quiescence. Knockdown of the enzyme that creates H4K20me3 results 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, results 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.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544 Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129 Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104 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.
Adam G
AG
Evertts
Amity L
AL
Manning
Xin
X
Wang
Nicholas J
NJ
Dyson
Benjamin A
BA
Garcia
Hilary A
HA
Coller
D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D002843:Chromatin / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology; D055785:Gene Knockdown Techniques; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D008938:Mitosis; D061251:Primary Cell Culture
D002843:Chromatin; D006657:Histones; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine