title: Light does not degrade the constitutively expressed BMAL1 protein in the mouse suprachiasmatic nucleus.
abstract: Biological rhythms in mammals are driven by a central circadian clock located in the suprachiasmatic nucleus (SCN). At the molecular level the biological clock is based on the rhythmic expression of clock genes. Two basic helix-loop-helix (bHLH)/PAS-containing transcription factors, CLOCK and BMAL1 (MOP3), provide the basic drive to the system by activating transcription of negative regulators through E box enhancer elements. A critical feature of circadian timing is the ability of the clockwork to be entrained to the environmental light/dark cycle. The light-resetting mechanism of the mammalian circadian clock is poorly understood. Light-induced phase shifts are correlated with the induction of the clock genes mPer1 and mPer2 and a subsequent increase in mPER1 protein levels. It has previously been suggested that rapid degradation of BMAL1 protein in the rat SCN is part of the resetting mechanism of the central pacemaker. Our study shows that BMAL1 and CLOCK proteins are continuously expressed at high levels in the mouse SCN, supporting the hypothesis that rhythmic negative feedback plays the major role in rhythm generation in the mammalian pacemaker. Using both immunocytochemistry and immunoblot analysis, our studies demonstrate that BMAL1 protein in the mouse SCN is not affected by a phase-resetting light pulse. These results indicate that rapid degradation of BMAL1 protein is not a consistent feature of resetting mechanisms in rodents.
authors.affiliation: Department of Neurobiology, Aaron Lazare Medical Research Building, Room 723, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605-2324, USA.
authors.forename: Charlotte
authors.initials: C
authors.lastname: von Gall
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Noton
authors.forename: Choogon
authors.initials: C
authors.lastname: Lee
authors.forename: David R
authors.initials: DR
authors.lastname: Weaver
mesh_terms: D056930:ARNTL Transcription Factors; D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D000918:Antibody Specificity; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000502:physiology; D016762:Genes, fos / Q000235:genetics; D005838:Genotype; D007091:Image Processing, Computer-Assisted; D015151:Immunoblotting; D007150:Immunohistochemistry; D008027:Light; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010477:Perfusion; D011233:Precipitin Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013493:Suprachiasmatic Nucleus / Q000378:metabolism* / Q000528:radiation effects*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000528:radiation effects*
chemical_list: D056930:ARNTL Transcription Factors; D000199:Actins; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C538961:Bmal1 protein, mouse; C538944:Clock protein, mouse; C538945:Clock protein, rat