Chromatin Regulation

SUV39H1 Drives Chromatin Structure

Science's STKE  15 Aug 2000:
Vol. 2000, Issue 45, pp. tw2
DOI: 10.1126/stke.2000.45.tw2

Modification of the histone proteins H4 and H3 occurs before changes in chromatin architecture. Whereas histone acetylation leads to greater DNA accessibility and transcription, histone methylation can also regulate the higher ordered structure of chromatin. Little is known of the mammalian proteins involved in the methylation of histones; however, Rea et al. have now identified a human protein termed SUV39H1 that methylates H3. In vitro methylation assays revealed that Lys9, located in the NH2-terminus of H3, is methylated in the presence of SUV39H1. Prior acetylation of Lys9 blocked Lys9 methylation, and phosphorylation of Ser10 blocked the ability of SUV39H1 to methylate Lys9 in vitro. Reciprocally, prior methylation of Lys9 decreased the ability of aurora kinase (which can phosphorylate Ser10 in H3) to use H3 as a substrate. However, prior acetylation of Lys9 (compared to an unacetylated control) increased the ability of aurora kinase to phosphorylate Ser10. This suggests that steric hindrance is not the reason that methylation and phosphorylation were antagonistic, but that H3 NH2-terminal modification events are interdependent. Fluorescence assays indicated that SUV39H-deficient cells had increased amounts of phosphorylated H3, supporting the observation that methylation of Lys9 blocked the phosphorylation of Ser10. Thus, having local regions of phosphorylated, acetylated, or methylated histones may contribute to epigenetic heritability of DNA states. A News & Views article by Paro discusses the role of catalytic domains in methyltransferases and the importance of histone modification.

Rea, S., Eisenhaber, F., O'Carroll, D., Strahl, B.D., Sun, Z.-W., Schmid, M., Opravil, S., Mechtler, K., Ponting, C.P., Allis, C.D., and Jenuwein, T. (2000) Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406: 593-599. [Online Journal]

Paro, R. (2000) Chromatin regulation: Formatting genetic text. Nature 406: 579-580. [Online Journal]