HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development. Cell Rep 2017 May 23;19(8):1602-1613
Date
05/26/2017Pubmed ID
28538179Pubmed Central ID
PMC5523860DOI
10.1016/j.celrep.2017.05.004Scopus ID
2-s2.0-85019679275 (requires institutional sign-in at Scopus site) 39 CitationsAbstract
The HAND2 transcriptional regulator controls cardiac development, and we uncover additional essential functions in the endothelial to mesenchymal transition (EMT) underlying cardiac cushion development in the atrioventricular canal (AVC). In Hand2-deficient mouse embryos, the EMT underlying AVC cardiac cushion formation is disrupted, and we combined ChIP-seq of embryonic hearts with transcriptome analysis of wild-type and mutants AVCs to identify the functionally relevant HAND2 target genes. The HAND2 target gene regulatory network (GRN) includes most genes with known functions in EMT processes and AVC cardiac cushion formation. One of these is Snai1, an EMT master regulator whose expression is lost from Hand2-deficient AVCs. Re-expression of Snai1 in mutant AVC explants partially restores this EMT and mesenchymal cell migration. Furthermore, the HAND2-interacting enhancers in the Snai1 genomic landscape are active in embryonic hearts and other Snai1-expressing tissues. These results show that HAND2 directly regulates the molecular cascades initiating AVC cardiac valve development.
Author List
Laurent F, Girdziusaite A, Gamart J, Barozzi I, Osterwalder M, Akiyama JA, Lincoln J, Lopez-Rios J, Visel A, Zuniga A, Zeller RAuthor
Joy Lincoln PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBase Sequence
Basic Helix-Loop-Helix Transcription Factors
Cell Movement
Chromatin
Endocardial Cushions
Epithelial-Mesenchymal Transition
Gene Expression Regulation, Developmental
Gene Regulatory Networks
Genome
Heart Valves
Mesoderm
Mice
Snail Family Transcription Factors
Transcription, Genetic