Journal article
Second heart field-specific expression of Nkx2-5 requires promoter proximal interaction with Srf
Mechanisms of development, Vol.162, pp.103615-103615
06/01/2020
DOI: 10.1016/j.mod.2020.103615
PMCID: PMC7525830
PMID: 32450132
Abstract
The cardiac homeobox transcription factor Nkx2-5 is a major determinant of cardiac identity and cardiac morphogenesis. Nkx2-5 operates as part of a complex and mutually reinforcing network of early transcription factors of the homeobox, GATA zinc finger and MADS domain families to initiate the program of cardiac development and differentiation, particularly in outflow tract precursor cells in the second heart field (SHF). We have now found evidence for another aspect of cardiac transcription factor cooperativity between Nkx2-5 and the cardiac enriched MADS domain transcription factor Srf. Specifically, Srf interaction with an evolutionarily conserved binding site in the Nkx2-5 CpG island-like proximal promoter is required for cardiac specific expression mediated by an SHF enhancer, and for combinatorial activation of these elements by cardiac transcription factors. These results provide further insight into cooperative gene regulation during cardiogenesis at the level of promoter-enhancer interactions.
•Cardiac development requires the cooperative action of multiple lineage-specific transcriptional regulators.•Nkx2-5 transcription factor is essential for early right heart development from second heart field.•Serum Response Factor (Srf)binds to a conserved promoter binding site and distal second heart field enhancer of Nkx2-5.•Loss of Srf binding to the Nkx2-5 promoter results in failure to maintain expression in differentiated right heart lineages.
Details
- Title: Subtitle
- Second heart field-specific expression of Nkx2-5 requires promoter proximal interaction with Srf
- Creators
- Christopher D. Clark - Medical University of South CarolinaKyu-Ho Lee - Medical University of South Carolina
- Resource Type
- Journal article
- Publication Details
- Mechanisms of development, Vol.162, pp.103615-103615
- DOI
- 10.1016/j.mod.2020.103615
- PMID
- 32450132
- PMCID
- PMC7525830
- NLM abbreviation
- Mech Dev
- ISSN
- 0925-4773
- eISSN
- 1872-6356
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 06/01/2020
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984696760902771
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