Publications

• Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage.

  Sanders S.L., Portoso M., Mata J., Baehler J., Allshire R.C., Kouzarides T.

  Histone lysine methylation is a key regulator of gene expression and heterochromatin function, but little is known as to how this modification impinges on other chromatin activities. Here we demonstrate that a previously uncharacterized SET domain protein, Set9, is responsible for H4-K20 methylati ... >> More

  Histone lysine methylation is a key regulator of gene expression and heterochromatin function, but little is known as to how this modification impinges on other chromatin activities. Here we demonstrate that a previously uncharacterized SET domain protein, Set9, is responsible for H4-K20 methylation in the fission yeast Schizosaccharomyces pombe. Surprisingly, H4-K20 methylation does not have any apparent role in the regulation of gene expression or heterochromatin function. Rather, we find the modification has a role in DNA damage response. Loss of Set9 activity or mutation of H4-K20 markedly impairs cell survival after genotoxic challenge and compromises the ability of cells to maintain checkpoint mediated cell cycle arrest. Genetic experiments link Set9 to Crb2, a homolog of the mammalian checkpoint protein 53BP1, and the enzyme is required for Crb2 localization to sites of DNA damage. These results argue that H4-K20 methylation functions as a "histone mark" required for the recruitment of the checkpoint protein Crb2. << Less

  Cell 119:603-614(2004) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.

• SETD4 regulates cell quiescence and catalyzes the trimethylation of H4K20 during diapause formation in Artemia.

  Dai L., Ye S., Li H.W., Chen D.F., Wang H.L., Jia S.N., Lin C., Yang J.S., Yang F., Nagasawa H., Yang W.J.

  As a prominent characteristic of cell life, the regulation of cell quiescence is important for proper development, regeneration, and stress resistance and may play a role in certain degenerative diseases. However, the mechanism underlying quiescence remains largely unknown. Encysted embryos of <i> ... >> More

  As a prominent characteristic of cell life, the regulation of cell quiescence is important for proper development, regeneration, and stress resistance and may play a role in certain degenerative diseases. However, the mechanism underlying quiescence remains largely unknown. Encysted embryos of <i>Artemia</i> are useful for studying the regulation of this state because they remain quiescent for prolonged periods during diapause, a state of obligate dormancy. In the present study, SET domain-containing protein 4, a histone lysine methyltransferase from <i>Artemia</i>, was identified, characterized, and named Ar-SETD4. We found that Ar-SETD4 was expressed abundantly in <i>Artemia</i> diapause embryos, in which cells were in a quiescent state. Meanwhile, trimethylated histone H4K20 (H4K20me3) was enriched in diapause embryos. The knockdown of Ar-SETD4 reduced the level of H4K20me3 significantly and prevented the formation of diapause embryos in which neither the cell cycle nor embryogenesis ceased. The catalytic activity of Ar-SETD4 on H4K20me3 was confirmed by an <i>in vitro</i> histone methyltransferase (HMT) assay and overexpression in cell lines. This study provides insights into the function of SETD4 and the mechanism of cell quiescence regulation. << Less

  Mol. Cell. Biol. 37:0-0(2017) [PubMed] [EuropePMC]