Editors' ChoiceCircadian Rhythms

When Is a Demethylase Not a Demethylase?

Science Signaling  04 Oct 2011:
Vol. 4, Issue 193, pp. ec275
DOI: 10.1126/scisignal.4193ec275

A transcriptional negative feedback mechanism is central to the mammalian circadian clock, but the detailed mechanisms that account for precise control of the oscillator (in particular, modifications to histones that influence transcription) are not fully understood. DiTacchio et al. (see the Perspective by Brown) show that regulation at the promoter of the Per2 gene, which encodes a clock component that in turn represses transcription of other genes, involves binding of a histone demethylase called JARID1a. The important function of JARID1a at the Per2 promoter, however, turned out not to depend on its histone demethylase activity but rather to be its influence to decrease histone acetylation at the Per promoter. Circadian rhythms were disrupted or altered in flies and mice lacking JARID1a.

L. DiTacchio, H. D. Le, C. Vollmers, M. Hatori, M. Witcher, J. Secombe, S. Panda, Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the circadian clock. Science 333, 1881–1885 (2011). [Abstract] [Full Text]

S. A. Brown, A new histone code for clocks? Science 333, 1833–1834 (2011). [Abstract] [Full Text]