DNA binding and transcriptional regulatory activity of mammalian achaete-scute homologous (MASH) proteins revealed by interaction with a muscle-specific enhancer.
The MASH genes are vertebrate homologues of achaete-scute, genes required for neuronal determination in Drosophila. The sequence of MASH1 and MASH2 contains a basic helix-loop-helix (bHLH) motif that is present in other transcriptional regulators such as MyoD and E12. In the absence of an authentic target for the MASH proteins, we examined their DNA binding and transcriptional regulatory activity by using a binding site (the E box) from the muscle creatine kinase (MCK) gene, a target of MyoD. Like myogenic bHLH proteins, the MASH proteins form heterooligomers with E12 that bind the MCK E box with high affinity in vitro. Unexpectedly, however, MASH1 and MASH2 also activate transcription of both exogenous and endogenous MCK in transfected C3H/10T1/2 fibroblasts. However, they do not induce myogenesis. Myogenic activity is not exclusively a property of the MyoD basic region, as substitution of this domain fails to confer myogenic activity on MASH1. These data suggest that different bHLH proteins may activate overlapping but distinct sets of target genes in the same cell type.
Johnson
J E
JE
Division of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena 91125.
Birren
S J
SJ
Saito
T
T
Anderson
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003402:Creatine Kinase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D007527:Isoenzymes; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics; D009132:Muscles / Q000502:physiology*; D017570:MyoD Protein; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D015500:Chloramphenicol O-Acetyltransferase; D003402:Creatine Kinase; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D009124:Muscle Proteins; D017570:MyoD Protein; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C489311:Ascl2 protein, mouse