title: Sequential Binding of MEIS1 and NKX2-5 on the Popdc2 Gene: A Mechanism for Spatiotemporal Regulation of Enhancers during Cardiogenesis.
abstract: The homeobox transcription factors NKX2-5 and MEIS1 are essential for vertebrate heart development and normal physiology of the adult heart. We show that, during cardiac differentiation, the two transcription factors have partially overlapping expression patterns, with the result that as cardiac progenitors from the anterior heart field differentiate and migrate into the cardiac outflow tract, they sequentially experience high levels of MEIS1 and then increasing levels of NKX2-5. Using the Popdc2 gene as an example, we also show that a significant proportion of target genes for NKX2-5 contain a binding motif recognized by NKX2-5, which overlaps with a binding site for MEIS1. Binding of the two factors to such overlapping sites is mutually exclusive, and this provides a simple regulatory mechanism for spatial and temporal synchronization of a common pool of targets between NKX2-5 and MEIS1.
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, the Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Laurent
authors.initials: L
authors.lastname: Dupays
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, the Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Shang
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, the Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Wilson
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, the Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Surendra
authors.initials: S
authors.lastname: Kotecha
authors.affiliation: Procedural Services Section, The Francis Crick Institute, Mill Hill Laboratory, the Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Wood
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, the Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Norma
authors.initials: N
authors.lastname: Towers
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, the Ridgeway, Mill Hill, London NW7 1AA, UK. Electronic address: tim.mohun@crick.ac.uk.
authors.forename: Timothy
authors.initials: T
authors.lastname: Mohun
mesh_terms: D000818:Animals; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian; D004742:Enhancer Elements, Genetic; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009206:Myocardium / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D059372:Nucleotide Motifs; D038081:Organogenesis / Q000235:genetics*; D011485:Protein Binding; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014336:Troponin / Q000235:genetics / Q000378:metabolism; D019210:Troponin I / Q000235:genetics / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C000616392:Meis1 protein, mouse; D009124:Muscle Proteins; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; C484469:Nkx2-5 protein, mouse; C498791:Popdc2 protein, mouse; D014157:Transcription Factors; D014336:Troponin; D019210:Troponin I; C587363:troponin T3, skeletal, fast, mouse