Cooperative Transcriptional Activation by the Neurogenic Basic Helix-Loop-Helix Protein MASH1 and Members of the Myocyte Enhancer Factor-2 (MEF2) Family

doi:10.1074/jbc.271.43.26659

Cooperative Transcriptional Activation by the Neurogenic Basic Helix-Loop-Helix Protein MASH1 and Members of the Myocyte Enhancer Factor-2 (MEF2) Family*

From the ^‡ Department of Molecular Biology and Oncology, Hamon Center for Basic Cancer Research, University of Texas Southwestern Medical Center, Dallas, Texas 75235 and the
^¶ Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

^∥ To whom correspondence should be addressed:
Dept. of Molecular Biology & Oncology, Hamon Center for Basic Cancer Research, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75235-9148
. Tel.: 214-648-1191; Fax: 214-648-1196; E-mail: eolson{at}hamon.swmed.edu

Abstract

Establishment of skeletal muscle and neural cell types is controlled by families of myogenic and neurogenic basic helix-loop-helix (bHLH) proteins, respectively. Myogenic bHLH proteins have been shown to activate skeletal muscle transcription in collaboration with members of the myocyte enhancer factor-2 (MEF2) family of MCM1-agamous-deficiens-serum response factor (MADS)-box transcription factors, which are expressed in differentiated myocytes and neurons. Here, we show that the neurogenic bHLH protein MASH1 interacts with members of the MEF2 family and that this interaction, mediated by the DNA binding and dimerization domains of these factors, results in synergistic activation of transcription through either the MASH1 or the MEF2 DNA binding site. Consistent with their involvement in activation of neuronal gene expression, members of the MEF2 family are expressed in P19 embryonal carcinoma cells that have been induced to form neurons following treatment with retinoic acid. These results suggest that members of the MEF2 family perform similar roles in synergistic activation of transcription in myogenic and neurogenic lineages by serving as cofactors for cell type-specific bHLH proteins.

Footnotes

↵^§ American Cancer Society postdoctoral fellow.
↵* This work was supported by grants from the National Institutes of Health, the Muscular Dystrophy Association, the Robert A. Welch Foundation, and the Human Sciences Frontiers Program (to E. N. O.). 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:

bHLH

basic helix-loop-helix

CAT

chloramphenicol acetyltransferase

DBD

DNA binding domain

DMEM

Dulbecco's modification of minimal essential medium

FCS

fetal calf serum

MADS

MCM1-agamous-deficiens-serum response factor

MASH

mammalian achaete-scute homolog

MCK

muscle creatine kinase

NCAM

neural cell adhesion molecule

RA

retinoic acid

PAGE

polyacrylamide gel electrophoresis

VP16

herpes virus virion protein 16

MEF2

myocyte enhancer factor-2.
↵² B. L. Black and E. N. Olson, unpublished observations.
- Received July 23, 1996.