Alternative splicing yields novel BMAL2 variants: tissue distribution and functional characterization.

Schoenhard JA, Eren M, Johnson CH, Vaughan DE
Am J Physiol Cell Physiol. 2002 283 (1): C103-14

PMID: 12055078 · DOI:10.1152/ajpcell.00541.2001

The BMAL2 gene encodes a member of the basic helix-loop-helix PER-ARNT-SIM family of transcription factors, which control diverse physiological processes including circadian rhythms. We identified four novel human BMAL2 transcripts that differ by alternative splicing within their NH2-terminal regions. Divergent expression of these and previously reported transcripts was observed among human tissues. The functional consequences of alternative splicing for transcriptional activation by CLOCK:BMAL2 heterodimers were assessed using luciferase reporter gene constructs that contained one of three diurnally regulated promoters, namely, those of the mouse period1, mouse vasopressin, and human plasminogen activator inhibitor-1 genes. These studies revealed that alternative splicing generates BMAL2 isoforms possessing high, medium, low, or no transcriptional activity. Similar results were obtained with each promoter, suggesting that alternative splicing may influence the amplitudes of both central and peripheral oscillators. Indeed, alternative splicing of BMAL2 may provide tissues with a rheostat capable of regulating CLOCK:BMAL2 heterodimer function across a broad continuum of potential transcriptional activities to accommodate varied metabolic demands and physiological roles.

MeSH Terms (32)

Alternative Splicing Amino Acid Sequence Animals ARNTL Transcription Factors Base Sequence Basic Helix-Loop-Helix Transcription Factors Cattle Cell Cycle Proteins Cells, Cultured Circadian Rhythm CLOCK Proteins Cryptochromes Drosophila Proteins Eye Proteins Flavoproteins Gene Deletion Genetic Variation Humans Mice Molecular Sequence Data Nuclear Proteins Peptide Fragments Period Circadian Proteins Photoreceptor Cells, Invertebrate Plasminogen Activator Inhibitor 1 Plasminogen Inactivators Receptors, G-Protein-Coupled Subcellular Fractions Tissue Distribution Trans-Activators Transcriptional Activation Transcription Factors

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