Methylation of Histone H3 on Lysine 4 by the Lysine Methyltransferase SET1 Protein Is Needed for Normal Clock Gene Expression

作者：Raduwan Hamidah; Isola Allison L; Belden William J^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288(12): 8380-8390.

DOI：10.1074/jbc.M112.359935

The circadian oscillator controls time-of-day gene expression by a network of interconnected feedback loops and is reset by light. The requisite for chromatin regulation in eukaryotic transcription necessitates temporal regulation of histone-modifying and chromatin-remodeling enzymes for proper clock function. CHD1is known to bindH3K4me3in mammalian cells, and Neurospora CHD1 is required for proper regulation of the frequency (frq) gene. Based on this, we examined a strain lacking SET1 to determine the role of H3K4 methylation in clock-and lightmediated frq regulation. Expression of frq was altered in strains lacking set1 under both circadian- and light-regulated gene expression. There is a delay in the phasing of H3K4me3 relative to the peak in frq expression. White Collar 2 (WC-2) association with the frq promoter persists longer in Delta set1, suggesting a more permissible chromatin state. Surprisingly, SET1 is required for DNA methylation in the frq promoter, indicating a dependence on H3K4me for DNA methylation. The data support a model where SET1 is needed for proper regulation by modulating chromatin at frq.

• 出版日期2013-3-22