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

American Journal of Physiology - Cell Physiology - Tập 283 Số 1 - Trang C103-C114 - 2002
John A. Schoenhard1, Mesut Eren2, Carl Hirschie Johnson3, Douglas E. Vaughan2,4
1Division of Cardiovascular Medicine, Departments of Medicine and Pharmacology, Vanderbilt University, Tennessee 37235, USA.
2Division of Cardiovascular Medicine, Departments of Medicine and Pharmacology, Vanderbilt University and
3Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235
4Veterans Affairs Medical Centers, Nashville 37232; and

Tóm tắt

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.

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10.1161/01.CIR.79.1.101

10.1126/science.289.5488.2344

10.1016/0169-328X(92)90133-V

10.1073/pnas.97.8.4339

10.1038/35057006

10.1016/S0002-9149(97)00181-1

10.1016/S0896-6273(00)80464-X

10.1016/0092-8674(92)90178-F

10.1126/science.280.5369.1564

10.1128/MCB.16.4.1706

10.1126/science.1852076

10.1074/jbc.272.13.8581

10.1523/JNEUROSCI.20-13-j0002.2000

10.1006/bbrc.1998.9275

10.1006/bbrc.1997.6371

10.1006/bbrc.2000.3248

10.1016/S0092-8674(00)80959-9

10.1016/0006-8993(95)00324-J

10.1016/S0092-8674(00)80245-7

10.1093/nar/12.2.857

10.1016/S0092-8674(00)81014-4

10.1161/01.CIR.91.5.1341

10.1074/jbc.271.35.21262

10.1016/S0092-8674(00)80473-0

10.1074/jbc.C000629200

10.1016/S0896-6273(00)80834-X

10.1161/hc4001.098048

10.1016/S0304-3940(01)01581-6

10.1046/j.1365-2443.2001.00462.x

10.1073/pnas.181228598

10.1128/MCB.14.9.6075

10.1146/annurev.physiol.63.1.647

10.1074/jbc.273.42.27039

10.1007/BF01197779

10.1046/j.1365-2443.2000.00363.x

10.1006/bbrc.1998.9012

10.1016/S0167-4781(00)00225-6

10.1073/pnas.85.15.5525

10.1016/0896-6273(95)90214-7

10.1007/s003359900797

10.1006/bbrc.1999.0970

10.1093/hmg/7.5.919

10.1073/pnas.94.2.713

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American Journal of Physiology - Cell Physiology

Tập 283 Số 1

C103-C114

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