Atrial Chamber-specific Expression of the Slow Myosin Heavy Chain 3 Gene in the Embryonic Heart

doi:10.1074/jbc.271.33.19836

Atrial Chamber-specific Expression of the Slow Myosin Heavy Chain 3 Gene in the Embryonic Heart*

From the Department of Medicine, Stanford University School of Medicine, Stanford, California 94305-5306

^‡To whom correspondence should be addressed. Tel.: 415-725-6449; Fax: 415-725-1420.

Abstract

The quail slow myosin heavy chain 3 (slow MyHC 3) gene is expressed in the developing heart and in slow muscles of the developing limb. It is first expressed in the pulsatile cardiac tube in the embryo, and as the heart chamberizes its expression becomes restricted to the atria. To identify regulatory elements responsible for atrial-specific expression, the 5′ upstream region of slow MyHC 3 gene was investigated. An atrial regulatory domain (ARD1) between −840 and −680 acts as an atrial cell-specific enhancer in primary cardiocyte cultures. ARD1 also specifies atrial-specific expression in vivo when the ARD1/heterologous promoter was introduced into developing chick embryos by a replication-competent retroviral vector. ARD1 is the first atrial cell-specific enhancer to be identified. Fine deletion and mutation analysis within ARD1 defined a 40-base pair vitamin D₃ receptor-like element that controls atrial cell-specific expression of the slow MyHC 3 gene by inhibiting its expression in ventricular cardiocytes.

Footnotes

↵* The work was supported by the National Institutes of Health Grant AG02822 and a grant from Muscular Dystrophy Association of America (to F. E. S.). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

MyHC

myosin heavy chain

ARD1

atrial regulatory domain 1

VDR

vitamin D₃ receptor

bp

base pairs

CAT

chloramphenicol acetyltransferase

CEF

chicken embryonic fibroblast

SV40

simian virus 40

MLC

myosin light chain

ANF

atrial natriuretic factor

AMHC

atrial-specific myosin heavy chain gene

mAb

monoclonal antibody

ED

embryonic day

PAGE

polyacrylamide gel electrophoresis

UTR

untranslated region.
↵²M. Schleinitz, and F. E. Stockdale, unpublished data.
- Received January 30, 1996.
- Revision received May 2, 1996.