Sequential binding of MEIS1 and NKX2-5 on the Popdc2 gene: a mechanism for spatiotemporal regulation of enhancers during cardiogenesis
Laurent Dupays
Catherine Shang
Robert Wilson
Surendra Kotecha
Sophie Wood
Norma Towers
Timothy Mohun
10779/crick.12681794.v1
https://crick.figshare.com/articles/journal_contribution/Sequential_binding_of_MEIS1_and_NKX2-5_on_the_Popdc2_gene_a_mechanism_for_spatiotemporal_regulation_of_enhancers_during_cardiogenesis/12681794
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.
2020-07-21 10:19:50
Animals
Binding Sites
Cell Adhesion Molecules
Embryo, Mammalian
Enhancer Elements, Genetic
Gene Expression Profiling
Gene Expression Regulation, Developmental
Homeobox Protein Nkx-2.5
Homeodomain Proteins
Mice
Mice, Transgenic
Molecular Sequence Data
Muscle Proteins
Myeloid Ecotropic Viral Integration Site 1 Protein
Myocardium
Neoplasm Proteins
Nucleotide Motifs
Organogenesis
Protein Binding
Signal Transduction
Transcription Factors
Troponin
Troponin I
Mohun U117562103
BRF
AS-ack
0601 Biochemistry and Cell Biology