Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the circadian clock.
Summary of "Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the circadian clock."
In animals, circadian oscillators are based on a transcription-translation circuit that revolves around the transcription factors CLOCK and BMAL1. We found that the JumonjiC (JmjC) and ARID domain-containing histone lysine demethylase 1a (JARID1a) formed a complex with CLOCK-BMAL1, which was recruited to the Per2 promoter. JARID1a increased histone acetylation by inhibiting histone deacetylase 1 function and enhanced transcription by CLOCK-BMAL1 in a demethylase-independent manner. Depletion of JARID1a in mammalian cells reduced Per promoter histone acetylation, dampened expression of canonical circadian genes, and shortened the period of circadian rhythms. Drosophila lines with reduced expression of the Jarid1a homolog, lid, had lowered Per expression and similarly altered circadian rhythms. JARID1a thus has a nonredundant role in circadian oscillator function.
Affiliation
Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Journal Details
This article was published in the following journal.
Name: Science (New York, N.Y.)
ISSN: 1095-9203
Pages: 1881-5
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21960634
- DOI: http://dx.doi.org/10.1126/science.1206022
Medical and Biotech [MESH] Definitions
Nuclear Receptor Subfamily 1, Group D, Member 1
A DNA-binding orphan nuclear receptor that negatively regulates expression of ARNTL TRANSCRIPTION FACTORS and plays a role as a regulatory component of the circadian clock system. The Nr1d1 nuclear receptor expression is cyclically-regulated by a feedback loop involving its positive regulation by CLOCK PROTEIN; BMAL1 PROTEIN heterodimers and its negative regulation by CRYPTOCHROME and PERIOD PROTEINS.
Clock Proteins
Basic helix-loop-helix (bHLH) domain-containing proteins that contain intrinsic HISTONE ACETYLTRANSFERASE activity and play important roles in CIRCADIAN RHYTHM regulation. Clock proteins combine with Arntl proteins to form heterodimeric transcription factors that are specific for E-BOX ELEMENTS and stimulate the transcription of several E-box genes that are involved in cyclical regulation. This transcriptional activation also sets into motion a time-dependent feedback loop which in turn down-regulates the expression of clock proteins.
Lysine-trna Ligase
An enzyme that activates lysine with its specific transfer RNA. EC 6.1.1.6.
Histone Demethylases
Enzymes that catalyse the removal of methyl groups from LYSINE or ARGININE residues found on HISTONES. Many histone demethylases generally function through an oxidoreductive mechanism.
Histone-lysine N-methyltransferase
An enzyme that catalyzes the methylation of the epsilon-amino group of lysine residues in proteins to yield epsilon mono-, di-, and trimethyllysine. EC 2.1.1.43.
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