Quantitative proteomic identification of MAZ as a transcriptional regulator of muscle-specific genes in skeletal and cardiac myocytes.

Molecular and Cellular Biology
Charis L HimedaStephen D Hauschka

Abstract

We identified a conserved sequence within the Muscle creatine kinase (MCK) promoter that is critical for high-level activity in skeletal and cardiac myocytes (MCK Promoter Element X [MPEX]). After selectively enriching for MPEX-binding factor(s) (MPEX-BFs), ICAT-based quantitative proteomics was used to identify MPEX-BF candidates, one of which was MAZ (Myc-associated zinc finger protein). MAZ transactivates the MCK promoter and binds the MPEX site in vitro, and chromatin immunoprecipitation analysis demonstrates enrichment of MAZ at the endogenous MCK promoter and other muscle gene promoters (Skeletal alpha-actin, Desmin, and alpha-Myosin heavy chain) in skeletal and cardiac myocytes. Consistent with its role in muscle gene transcription, MAZ transcripts and DNA-binding activity are upregulated during skeletal myocyte differentiation. Furthermore, MAZ was shown to bind numerous sequences (e.g., CTCCTCCC and CTCCACCC) that diverge from the GA box binding motif. Alternate motifs were identified in many muscle promoters, including Myogenin and MEF2C, and one motif was shown to be critical for Six4 promoter activity in both skeletal and cardiac myocytes. Interestingly, MAZ occupies and is able to transactivate the Six4 promoter in...Continue Reading

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Citations

Feb 10, 2011·Molecular Genetics and Genomics : MGG·Shuang ZhangJudith K Davie
Mar 3, 2010·The Journal of Biological Chemistry·Richard W TsikaJuan Ji
Apr 21, 2010·Molecular and Cellular Biology·Charis L HimedaStephen D Hauschka
Aug 23, 2011·Therapeutic Advances in Chronic Disease·Julie A WolframHyoung-Gon Lee
Jul 30, 2011·Skeletal Muscle·Phillip Wl TaiStephen D Hauschka
Jan 6, 2009·Immunological Reviews·Daniel E Zak, Alan Aderem
Sep 26, 2013·Journal of Proteomics·A TachenyP Renard
Sep 17, 2013·Developmental Biology·Charis L HimedaCharles P Emerson
Feb 8, 2013·Proceedings of the National Academy of Sciences of the United States of America·Hamid MirzaeiJeffrey Ranish
Dec 30, 2014·Journal of Proteome Research·Nina C HubnerHendrik G Stunnenberg
Apr 18, 2009·Analytical Chemistry·Mohamed Abu-FarhaDaniel Figeys
Aug 6, 2021·Blood Advances·Darya DeenDouglas Vernimmen

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