title: The transcription factor Mesp1 interacts with cAMP-responsive element binding protein 1 (Creb1) and coactivates Ets variant 2 (Etv2) gene expression.
abstract: Mesoderm posterior 1 (Mesp1) is well recognized for its role in cardiac development, although it is expressed broadly in mesodermal lineages. We have previously demonstrated important roles for Mesp1 and Ets variant 2 (Etv2) during lineage specification, but their relationship has not been defined. This study reveals that Mesp1 binds to the proximal promoter and transactivates Etv2 gene expression via the CRE motif. We also demonstrate the protein-protein interaction between Mesp1 and cAMP-responsive element binding protein 1 (Creb1) in vitro and in vivo. Utilizing transgenesis, lineage tracing, flow cytometry, and immunostaining technologies, we define the lineage relationship between Mesp1- and Etv2-expressing cell populations. We observe that the majority of Etv2-EYFP(+) cells are derived from Mesp1-Cre(+) cells in both the embryo and yolk sac. Furthermore, we observe that the conditional deletion of Etv2, using a Mesp1-Cre transgenic strategy, results in vascular and hematopoietic defects similar to those observed in the global deletion of Etv2 and that it has embryonic lethality by embryonic day 9.5. In summary, our study supports the hypothesis that Mesp1 is a direct upstream transactivator of Etv2 during embryogenesis and that Creb1 is an important cofactor of Mesp1 in the transcriptional regulation of Etv2 gene expression.
authors.affiliation: From the Lillehei Heart Institute, Medical School, University of Minnesota, Minneapolis, Minnesota 55455 and.
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Shi
authors.affiliation: From the Lillehei Heart Institute, Medical School, University of Minnesota, Minneapolis, Minnesota 55455 and.
authors.forename: Katie M
authors.initials: KM
authors.lastname: Zirbes
authors.affiliation: From the Lillehei Heart Institute, Medical School, University of Minnesota, Minneapolis, Minnesota 55455 and.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Rasmussen
authors.affiliation: the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Anwarul
authors.initials: A
authors.lastname: Ferdous
authors.affiliation: From the Lillehei Heart Institute, Medical School, University of Minnesota, Minneapolis, Minnesota 55455 and.
authors.forename: Mary G
authors.initials: MG
authors.lastname: Garry
authors.affiliation: From the Lillehei Heart Institute, Medical School, University of Minnesota, Minneapolis, Minnesota 55455 and.
authors.forename: Naoko
authors.initials: N
authors.lastname: Koyano-Nakagawa
authors.affiliation: From the Lillehei Heart Institute, Medical School, University of Minnesota, Minneapolis, Minnesota 55455 and garry@umn.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Garry
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D049452:Green Fluorescent Proteins; D014157:Transcription Factors; C492004:Creb1 protein, mouse; C503994:ER71 protein, mouse; C101538:Mesp1 protein, mouse
keywords: Basic Helix-Loop-Helix Transcription Factor (bHLH); ETS Transcription Factor Family; Protein-Protein Interaction; Transcription Regulation; Transcriptional Coactivator