Functional analysis of a novel clock gene Bmal2.

Accession number;02A0472907
Title;Functional analysis of a novel clock gene Bmal2.
Author; IKEDA MASAAKI (Saitamaidai Seirigaku) EBISAWA TAKASHI (Saitamaidai Seishin'igaku) KUMAGAI MEGUMI (Saitamaidai Seirigaku) HONMA SATO (Hokudai Igakukenkyuka Sogoseiri) SHIMIZU NOBUYOSHI (Keiodai I Bunshiseibutsugaku) HONMA KEN'ICHI (Hokudai Igakukenkyuka Sogoseiri) TAKAHASHI KIYOHISA (Natl. Center of Neurol. and Psychiatry) YAMAUCHI TOSHIO (Saitamaidai Seishin'igaku) NOMURA MASAHIKO (Saitamaidai Seirigaku)
Journal Title;Annual Report of the Pharmacopsychiatry Research Foundation
Journal Code:Y0939A
ISSN:0286-7591
VOL.;NO.34;PAGE.279-286(2002)
Figure&Table&Reference;FIG.4, REF.21
Pub. Country;Japan
Language;Japanese
Abstract;Recent progress in the research on molecular clock system revealed that the molecular basis of circadian clock generation is transcriptional control of clock-related genes. We have cloned a novel bHLH-PAS factor and named Brain and muscle Arnt-like protein 1 (Bmal1). In the circadian system, Bmal1 acts as a positive element within a transcription-translation negative feedback loop and is an essential component of the mammalian circadian pacemaker. To identify all members of bHLH-PAS factors involved in circadian system, we cloned a novel bHLH-PAS factor and named Bmal2. The extent of the corresponding sequences of ORF identity between Bmal2 and Bmal1 is 56%, and overall amino acid identity is 49%. Human Bmal2 mRNA was expressed in human fetal brain and adult liver. mBmal2 mRNA was expressed in the hippocampus, cerebral cortex and pyiriform cortex. The circadian rhythm of mBmal2 mRNA was not robust in the suprachiasmatic nuclei. Bmal2 interacted with Clock as determined by yeast two-hybrid interaction assay. Coexpression of Bmal2 and Clock synergistically activated expression of the reporter gene containing 3E-boxes in the promoter region of mPer1. Understanding the function of clock genes and involvement of clock genes in disorders of the human circadian system promise for development innovative treatment strategies for a wide range of clinical disorders. (author abst.)