Myomaxin is a novel transcriptional target of MEF2A that encodes a Xin-related alpha-actinin-interacting protein.
The physiological targets regulated by MEF2 in striated muscle are not completely known. Several recent studies have identified novel downstream target genes and shed light on the global transcriptional network regulated by MEF2 in muscle. In our continuing effort to identify novel, downstream pathways controlled by MEF2, we have used mef2a knock-out mice to find those genes dependent on MEF2A transcriptional activity. Here, we describe the characterization of a direct, downstream target gene for the MEF2A transcription factor encoding a large, muscle-specific protein that localizes to the Z-disc/costameric region in striated muscle. This gene, called myomaxin, was identified as a gene markedly down-regulated in MEF2A knock-out hearts. Myomaxin is the mouse ortholog of a partial human cDNA of unknown function named cardiomyopathy associated gene 3 (CMYA3). Myomaxin is expressed as a single, large transcript of approximately 11 kilobases in adult heart and skeletal muscle with an open reading frame of 3,283 amino acids. The protein encoded by the myomaxin gene is related to the actin-binding protein Xin and interacts with the sarcomeric Z-disc protein, alpha-actinin-2. Our findings demonstrate that Myomaxin functions directly downstream of MEF2A at the peripheral Z-disc complex in striated muscle potentially playing a role in regulating cytoarchitectural integrity.
Huang
Hsuan-Ting
HT
Department of Biology, Program in Cell and Molecular Biology, Boston University, Boston, Massachusetts 02215, USA.
Brand
Ondra M
OM
Mathew
Matthen
M
Ignatiou
Christos
C
Ewen
Elizabeth P
EP
McCalmon
Sarah A
SA
Naya
Francisco J
FJ
D000185:Actinin / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D060588:LIM Domain Proteins; D064326:MEF2 Transcription Factors; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018006:Myogenic Regulatory Factors / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D012689:Sequence Homology, Nucleic Acid
D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D064326:MEF2 Transcription Factors; C578036:Mef2a protein, mouse; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins; C500305:XIRP2 protein, mouse; C118478:Xin protein, mouse; D000185:Actinin