Disease relevance of Bhlhb3

• Stra13 is expressed in embryonic as well as adult tissues derived from neuroectoderm, mesoderm, and endoderm and has been associated with response to hypoxia, suggesting a complex role for this protein and the highly related Sharp1/Dec2 protein in homeostatic regulation [1].

High impact information on Bhlhb3

• Our previous studies have shown that the bHLH factor Sharp-1 is expressed in skeletal muscle and interacts with MyoD and E-proteins [2].
• Sharp-1/DEC2 inhibits skeletal muscle differentiation through repression of myogenic transcription factors [2].
• We report here that endogenous Sharp-1 is expressed in proliferating C2C12 myoblasts and is down-regulated during myogenic differentiation [2].
• Constitutive expression of Sharp-1 in C2C12 myoblasts promotes cell cycle exit causing a decrease in cyclin D1 expression but blocks terminal differentiation [2].
• In this study, we have characterized the DNA-binding and transcriptional properties of the bHLH factor mSharp-1/DEC2. mSharp-1 belongs to the Hairy/Enhancer of Split subfamily of bHLH factors and exhibits the highest structural and sequence identity with Stra13 [3].

Biological context of Bhlhb3

• DEC1 and DEC2 can inhibit CLOCK:BMAL1 transactivation of the clock gene Per1, suggesting that these transcription factors may help regulate circadian timing [4].
• These data point to up-regulation of Dec1 and Dec2 by Clock in vivo [4].
• The genes Dec1 and Dec2 are expressed rhythmically in the rat suprachiasmatic nuclei, and Dec1 expression is stimulated by light in a time-dependent manner with the kinetics of an immediate early gene [4].
• The DEC2 gene was mapped to human chromosome 12p11.23-p12.1, mouse chromosome 6 G2-G3 and rat chromosome 4q43 distal-q4, where the conserved linkage homology has been identified among these species [5].
• It is known that mammalian circadian rhythms are regulated by molecular clockwork systems based on a negative-feedback loop, and CLOCK/BMAL1 and CLOCK/BMAL2 enhance DEC2 transcription via CACGTG E-boxes [6].

Anatomical context of Bhlhb3

• However, circadian expression of Dec1 in liver and kidney and that of Dec2 in skeletal muscle of Clock mutant mice suggested that CLOCK-independent circadian regulation operates in some tissues [7].
• During mouse mammary gland development in vivo, Stra13 is highly expressed in epithelial ducts during puberty, and strongly induced in both ducts and alveoli during early involution, while the related Sharp-1 gene is highly expressed only during late stages of involution [8].
• The basic helix-loop-helix (bHLH) transcription factors, DEC2 and DEC1, play critical roles in the circadian rhythm of the suprachiasmatic nucleus (SCN) [6].
• DEC1 (differentially expressed in chondrocytes 1) and DEC2 are E-box-binding transcription factors and exhibit a circadian expression pattern [9].

Associations of Bhlhb3 with chemical compounds

• DEC2 had high (97%) and moderate (52%) similarities in the bHLH region and the Orange domain with DEC1, respectively [5].
• To understand the role of arginine 57 ((57)Arg) within the basic region of DEC2, we examined the effect of substituting this residue into DEC2 on CLOCK/BMAL2-mediated transactivation [6].

Physical interactions of Bhlhb3

• Previous studies with mouse DEC2 showed that this factor interacts with Sp1 [9].

Other interactions of Bhlhb3

• Dec1 becomes arrhythmic; Dec2 remains weakly rhythmic in a 12L:12D light-dark cycle but is arrhythmic in constant darkness [4].
• We demonstrate that the interaction of Sharp-1 with MyoD and E-proteins results in reduced DNA binding and transactivation from MyoD-dependent E-box sites [2].
• 57Arg in the bHLH transcription factor DEC2 is essential for the suppression of CLOCK/BMAL2-mediated transactivation [6].

Analytical, diagnostic and therapeutic context of Bhlhb3

• Molecular cloning and characterization of DEC2, a new member of basic helix-loop-helix proteins [5].
• We also showed that proteins which were wild-type and substitution mutants of DEC2 were expressed at nearly equivalent levels by Western blotting [6].

References