Functional and Physical Interactions between Mammalian Achaete-Scute Homolog 1 and Myocyte Enhancer Factor 2A

doi:10.1074/jbc.271.24.14371

Functional and Physical Interactions between Mammalian Achaete-Scute Homolog 1 and Myocyte Enhancer Factor 2A*

From the Department of Cardiology, Children's Hospital, and
^§ Department of Cell Biology and Pediatrics, Harvard Medical School, Boston, Massachusetts 02115

^‡ Supported by a Howard Hughes Medical Institute Postdoctoral Fellowship and by National Institutes of Health, NINDS Developmental Research Training Grant in Neurobiology 5-T32-NS07009-16. To whom correspondence should be addressed:
Division of Neuroscience, Children's Hospital, and Department of Neurobiology, Harvard Medical School, Boston, MA 02115.
Tel.: 617-355-4361; Fax: 617-738-1542.

Abstract

The mammalian achaete-scute homolog 1 (MASH1) protein is required for the early development of the nervous system. However, the molecular and biochemical mechanism by which MASH1 acts to determine neurogenesis are still unknown. The myocyte enhancer factor 2A (MEF2A) is a MADS transcription factor that is essential for the specification and differentiation of the muscle lineage. Here we show that MEF2A and MASH1 are coordinately induced during the differentiation of the teratocarcinoma cell line P19 along a neuronal lineage and that in transient transfection assays, MEF2A and MASH1 cooperatively activate gene expression. This cooperativity appears to be due to a specific physical interaction between MEF2A and MASH1. Taken together, these findings suggest that MASH1 via a cooperative interaction with MEF2A may regulate the expression of specific genes that are critical for neuronal differentiation.

Footnotes

↵* This work had been supported in part by grants from Howard Hughes Medical Institute. 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:

MEF2

myocyte enhancer factor 2

MASH1

the mammalian achaete-scute homolog 1

CAT

chloramphenicol acetyltransferase

GST

glutathione S-transferase

PAGE

polyacrylamide gel electrophoresis.
↵² Z. Mao and B. Nadal-Ginard, unpublished data.
- Received February 6, 1996.