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This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/H3065    most recent 01224.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Giger, J. Articles by Haddad, F. Search for Related Content PubMed PubMed Citation Articles by Giger, J. Articles by Haddad, F.

Activity of the -myosin heavy chain antisense promoter responds to diabetes and hypothyroidism

Department of Physiology and Biophysics, University of California, Irvine, California

Submitted 6 November 2006 ; accepted in final form 15 February 2007

Two genes encoding cardiac myosin heavy chain (MHC) isoforms, and , are arranged in tandem 4.5 kb apart. We examined pre-mRNA and mature mRNA levels of and genes in control, diabetic (streptozotocin), hypothyroid (propylthiouracil), and hyperthyroid rat hearts and analyzed the naturally occurring antisense (AS) RNA species that starts in the middle of the 4.5-kb intergenic region and extends upstream to the -gene promoter. The and genes are expressed antithetically in control, diabetic, hypothyroid, and hyperthyroid hearts. Expression of AS -RNA was positively correlated with -mRNA and negatively correlated with sense mRNA. These results support the novel idea of common promoter-regulatory elements situated in the intergenic region that likely control transcription of both sense and AS genes and that AS transcription negatively regulates -MHC gene expression. To test whether an intergenic promoter drives transcription of AS RNA, a 1340-bp sequence of the intergenic region was inserted into a luciferase plasmid in the 3'-to-5' AS direction and was injected into rat ventricle. This promoter was activated in control heart and decreased greatly in response to propylthiouracil and streptozotocin and increased in hyperthyroid rats, similar in pattern to the endogenous AS RNA. When a putative retinoic acid receptor (RAR) site (a known thyroid hormone receptor cofactor) in this promoter was mutated, the reporter activity was almost abolished in control, propylthiouracil, and streptozotocin hearts. We conclude that there is an intergenic promoter that is active in the AS direction and that the putative RAR element is a vital regulatory site.

mRNA; hyperthyroidism; in vivo gene injection; retinoic acid receptor; peroxisome proliferator-activated receptor

This article has been cited by other articles:

				D. L. Allen Making sense (and antisense) of myosin heavy chain gene expression. Comments on "Intergenic bidirectional promoter and cooperative regulation of the IIx and IIb MHC genes in fast skeletal muscle" by Rinaldi et al. Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2008; 295(1): R206 - R207. [Full Text] [PDF]

				F. Haddad, A. X. Qin, P. W. Bodell, W. Jiang, J. M. Giger, and K. M. Baldwin Intergenic transcription and developmental regulation of cardiac myosin heavy chain genes Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H29 - H40. [Abstract] [Full Text] [PDF]