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

• Published in: The Journal of biological chemistry 2013-03, Vol.288 (12), p.8380-8390
• Main Authors: Raduwan, Hamidah, Isola, Allison L., Belden, William J.
• Format: Article
• Language: English
• Subjects: Chromatin Immunoprecipitation (ChIP); Chromatin Modification; Circadian Rhythm; Circadian Rhythms; DNA Methylation; DNA-Binding Proteins - metabolism; Epigenesis, Genetic; Fungal Proteins - genetics; Fungal Proteins - metabolism; Fungal Proteins - physiology; Gene Expression Regulation, Fungal - radiation effects; Gene Knockout Techniques; Gene Regulation; Histone-Lysine N-Methyltransferase - genetics; Histone-Lysine N-Methyltransferase - metabolism; Histone-Lysine N-Methyltransferase - physiology; Histones - metabolism; Light; Methylation; Neurospora; Neurospora crassa - enzymology; Neurospora crassa - genetics; Neurospora crassa - physiology; Neurospora crassa - radiation effects; Protein Processing, Post-Translational; Spores, Fungal - enzymology; Spores, Fungal - genetics; Spores, Fungal - physiology; Spores, Fungal - radiation effects; Transcription Factors - metabolism
• ISSN: 0021-9258; 1083-351X
• 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. CHD1 is known to bind H3K4me3 in 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 light-mediated 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 Δset1, 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. Background: Eukaryotic circadian clocks require chromatin modifications and remodeling. Results: SET1 is required for proper expression of the Neurospora clock gene frequency (frq). SET1 modifies chromatin at frq with the peak in H3K4me3 occurring after the peak in activation. Conclusion: H3K4 methylation appears to mitigate White Collar complex (WCC)-mediated expression. Significance: Chromatin is a key component underlying circadian oscillations in gene expression.