The Arabidopsis LDL1/2-HDA6 histone modification complex is functionally associated with CCA1/LHY in regulation of circadian clock genes

Abstract In Arabidopsis, the circadian clock central oscillator genes are important cellular components to generate and maintain circadian rhythms. There is a negative feedback loop between the morning expressed CCA1 (CIRCADIAN CLOCK ASSOCIATED 1)/LHY (LATE ELONGATED HYPOCOTYL) and evening expressed TOC1 (TIMING OF CAB EXPRESSION 1). CCA1 and LHY negatively regulate the expression of TOC1, while TOC1 also binds to the promoters of CCA1 and LHY to repress their expression. Recent studies indicate that histone modifications play an important role in the regulation of the central oscillators. However, the regulatory relationship between histone modifications and the circadian clock genes remains largely unclear. In this study, we found that the Lysine-Specific Demethylase 1 (LSD1)-like histone demethylases, LDL1 and LDL2, can interact with CCA1/LHY to repress the expression of TOC1. ChIP-Seq analysis indicated that LDL1 targets a subset of genes involved in the circadian rhythm regulated by CCA1. Furthermore, LDL1 and LDL2 interact with the histone deacetylase HDA6 and co-regulate TOC1 by histone demetylation and deacetylaion. These results provide new insight into the molecular mechanism of how the circadian clock central oscillator genes are regulated through histone modifications.