User:User:Marcia Ivonne Peña Paz
From Proteopedia
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BMAL_1
Brain and muscle Arnt (aryl hydrocarbon receptor nuclear translocator)like 1. Also known as MOP3.
Bmal1 is a 626 amino acids, transcription factor of the basic helix-loop-helix (bHLH) - PAS family[1]. It is also a major component of both central and peripheral clock, it is part of the transcriptional/translational feed back loop of the circadian timing system.
Gene regulation and expression
It is encoded by the ARNTL / BMAL1 gene in humans and rodents. It maps to human chromosome 11p15.2. It has different splicing variants, but two isoforms have been found to have differnt initiation codon.[1]. It has been reported that it is dominantly expressed at high levels in some areas of the brain, skeletal muscle, cardiac muscle, but it is also expressed in other tissues such as liver or pancreas. [2] [3] [4]
Bmal1 function
Bmal1 is a core component of the circadian clock, it is also an important element of the circadian pacemaker. It forms an heterodimer with CLOCK or NPAS2 and both translocate into the nucleus. The heterodimer formed in the cytoplasm migrates to the nucleus where it binds to E-box promoter of target genes, acting as the positive feedback. They promote the transcription of Per and Cry genes, whose proteins form the negative feed back loop, they heterodimerize and repress CLOCK-BMAL1 complex activity.
CLOCK-BMAL1 complex regulate clock-controlled genes, modulating food intake, hormonal synthesis, body temperature and metabolism. It modulates the expression of the genes RevErbα (nuclear repressor), Dbp (D site albumin promoter)Cry 1/2, Per 1/2/3, Dbp, Rorα, Pparα, Namt, Ccg, MyoD, CKIε.
Pathologies associated with BMAL1
Studies have reported that disruption of circadian rhythms in mice has a role in reduced lifespan, reduced body weight, and decreased activity levels. Kondratov et al. have demonstrated it in their Bmal 1 KO model. [5]
As reported by Andrews et al, [6] Bmal1 KO mice have decreased force, shown in whole muscle as in single fibers. They also have altered myofibrilar architecture.
Studies in rats and humans suggest that there is a relationship between Bmal1 polymorphisms and hypertension [7]. Disruption of circadian oscillation of glucose metabolism has been related to type 2 diabetis.[8]
