title: Genome-Wide Identification of MESP1 Targets Demonstrates Primary Regulation Over Mesendoderm Gene Activity.
abstract: MESP1 is considered the first sign of the nascent cardiac mesoderm and plays a critical role in the appearance of cardiac progenitors, while exhibiting a transient expression in the developing embryo. We profiled the transcriptome of a pure population of differentiating MESP1-marked cells and found that they chiefly contribute to the mesendoderm lineage. High-throughput sequencing of endogenous MESP1-bound DNA revealed that MESP1 preferentially binds to two variants of E-box sequences and activates critical mesendoderm modulators, including Eomes, Gata4, Wnt5a, Wnt5b, Mixl1, T, Gsc, and Wnt3. These mesendoderm markers were enriched in the MESP1 marked population before the appearance of cardiac progenitors and myocytes. Further, MESP1-binding is globally associated with H(3)K(27) acetylation, supporting a novel pivotal role of it in regulating target gene epigenetics. Therefore, MESP1, the pioneer cardiac factor, primarily directs the appearance of mesendoderm, the intermediary of the earliest progenitors of mesoderm and endoderm organogenesis.
authors.affiliation: Texas Heart Institute, Texas Medical Center, Houston, Texas, USA.|Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Soibam
authors.affiliation: Texas Heart Institute, Texas Medical Center, Houston, Texas, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Benham
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.
authors.forename: Jong
authors.initials: J
authors.lastname: Kim
authors.affiliation: The Institute of Biosciences and Technology, Texas A & M University Health Science Center, Houston, Texas, USA.
authors.forename: Kuo-Chan
authors.initials: KC
authors.lastname: Weng
authors.affiliation: Texas Heart Institute, Texas Medical Center, Houston, Texas, USA.
authors.forename: Litao
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Xueping
authors.initials: X
authors.lastname: Xu
authors.affiliation: Texas Heart Institute, Texas Medical Center, Houston, Texas, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Robertson
authors.affiliation: Texas Heart Institute, Texas Medical Center, Houston, Texas, USA.
authors.forename: Alon
authors.initials: A
authors.lastname: Azares
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Austin J
authors.initials: AJ
authors.lastname: Cooney
authors.affiliation: Texas Heart Institute, Texas Medical Center, Houston, Texas, USA.|Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schwartz
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002461:Cell Line, Transformed; D019070:Cell Lineage / Q000502:physiology; D053595:Embryonic Stem Cells / Q000502:physiology; D004707:Endoderm / Q000196:embryology / Q000502:physiology*; D018390:Gene Targeting / Q000379:methods; D055106:Genome-Wide Association Study / Q000379:methods*; D008297:Male; D008648:Mesoderm / Q000196:embryology / Q000502:physiology*; D051379:Mice; D032383:Myocytes, Cardiac / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C101538:Mesp1 protein, mouse
keywords: Cell signaling; Developmental biology; Differentiation; Embryonic stem cells; Genomics