title: Myocardin-related transcription factors are required for cardiac development and function.
abstract: Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the developing or adult heart has not been explored. Through cardiac-specific deletion of MRTF alleles in mice, we show that either MRTF-A or MRTF-B is dispensable for cardiac development and function, whereas deletion of both MRTF-A and MRTF-B causes a spectrum of structural and functional cardiac abnormalities. Defects observed in MRTF-A/B null mice ranged from reduced cardiac contractility and adult onset heart failure to neonatal lethality accompanied by sarcomere disarray. RNA-seq analysis on neonatal hearts identified the most altered pathways in MRTF double knockout hearts as being involved in cytoskeletal organization. Together, these findings demonstrate redundant but essential roles of the MRTFs in maintenance of cardiac structure and function and as indispensible links in cardiac cytoskeletal gene regulatory networks.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States.
authors.forename: Mayssa H
authors.initials: MH
authors.lastname: Mokalled
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States; Hamon Center for Regenerative Science and Medicine University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States.
authors.forename: Kelli J
authors.initials: KJ
authors.lastname: Carroll
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States; Hamon Center for Regenerative Science and Medicine University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States.
authors.forename: Bercin K
authors.initials: BK
authors.lastname: Cenik
authors.affiliation: Hamon Center for Regenerative Science and Medicine University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States; Department of Clinical Sciences, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States.
authors.forename: Beibei
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States; Hamon Center for Regenerative Science and Medicine University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States; Hamon Center for Regenerative Science and Medicine University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States.
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States; Hamon Center for Regenerative Science and Medicine University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States.
authors.forename: Rhonda
authors.initials: R
authors.lastname: Bassel-Duby
mesh_terms: D000818:Animals; D001483:Base Sequence; D003599:Cytoskeleton / Q000502:physiology; D004452:Echocardiography; D053263:Gene Regulatory Networks / Q000502:physiology*; D006321:Heart / Q000196:embryology* / Q000502:physiology; D006652:Histological Techniques; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D012518:Sarcomeres / Q000378:metabolism / Q000502:physiology*; D017423:Sequence Analysis, RNA; D026362:Serum Response Factor / Q000378:metabolism*; D015534:Trans-Activators / Q000172:deficiency / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*
chemical_list: C511173:Mrtfa protein, mouse; D026362:Serum Response Factor; D015534:Trans-Activators; D014157:Transcription Factors; C503315:myocardin-related transcription factor B, mouse
keywords: Cardiac morphogenesis; Cytoskeletal dynamics; Heart function; MRTF-A/MKL1; MRTF-B/MKL2; Sarcomere arrangement