Transcription Enhancer Factor 1 Binds Multiple Muscle MEF2 and A/T-Rich Elements during Fast-to-Slow Skeletal Muscle Fiber Type Transitions
Autor: | Juan Ji, Richard W. Tsika, Aijing Zhang, Natalia G. Karasseva, Gretchen L. Tsika, Xiaoqing Mao |
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Rok vydání: | 2003 |
Předmět: |
Oligonucleotides
Mice Cytosol Genes Reporter Protein Isoforms Luciferases Promoter Regions Genetic MEF2 Transcription Factors Myogenesis Nuclear Proteins TEA Domain Transcription Factors DNA-Binding Proteins Muscle Fibers Slow-Twitch medicine.anatomical_structure Myogenic Regulatory Factors Muscle Fibers Fast-Twitch Plasmids Protein Binding Transcriptional Activation Mef2 Gene isoform DNA Complementary Blotting Western Molecular Sequence Data Biology Transfection Thymidine Kinase Cell Line Two-Hybrid System Techniques medicine Animals Humans Electrophoretic mobility shift assay Muscle Skeletal Enhancer Molecular Biology Transcription factor Gene Library Cell Nucleus Transcriptional Regulation Binding Sites Base Sequence Models Genetic Skeletal muscle Cell Biology Blotting Northern Molecular biology Rats Mutagenesis Desmin Transcription Factors |
Zdroj: | Molecular and Cellular Biology. 23:5143-5164 |
ISSN: | 1098-5549 |
DOI: | 10.1128/mcb.23.15.5143-5164.2003 |
Popis: | In adult mouse skeletal muscle, beta-myosin heavy chain (betaMyHC) gene expression is primarily restricted to slow type I fibers; however, its expression can be induced in fast type II fibers in response to a sustained increase in load-bearing work (mechanical overload [MOV]). Our previous betaMyHC transgenic and protein-DNA interaction studies have identified an A/T-rich element (betaA/T-rich -269/-258) that is required for slow muscle expression and which potentiates MOV responsiveness of a 293-bp betaMyHC promoter (beta293wt). Despite the GATA/MEF2-like homology of this element, we found binding of two unknown proteins that were antigenically distinct from GATA and MEF2 isoforms. By using the betaA/T-rich element as bait in a yeast one-hybrid screen of an MOV-plantaris cDNA library, we identified nominal transcription enhancer factor 1 (NTEF-1) as the specific betaA/T-rich binding factor. Electrophoretic mobility shift assay analysis confirmed that NTEF-1 represents the enriched binding activity obtained only when the betaA/T-rich element is reacted with MOV-plantaris nuclear extract. Moreover, we show that TEF proteins bind MEF2 elements located in the control region of a select set of muscle genes. In transient-coexpression assays using mouse C2C12 myotubes, TEF proteins transcriptionally activated a 293-bp betaMyHC promoter devoid of any muscle CAT (MCAT) sites, as well as a minimal thymidine kinase promoter-luciferase reporter gene driven by three tandem copies of the desmin MEF2 or palindromic Mt elements or four tandem betaA/T-rich elements. These novel findings suggest that in addition to exerting a regulatory effect by binding MCAT elements, TEF proteins likely contribute to regulation of skeletal, cardiac, and smooth muscle gene networks by binding select A/T-rich and MEF2 elements under basal and hypertrophic conditions. |
Databáze: | OpenAIRE |
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