Journal article
The Basic-Helix-Loop-Helix Transcription Factor HAND2 Directly Regulates Transcription of the Atrial Naturetic Peptide Gene
Journal of molecular and cellular cardiology, Vol.34(10), pp.1335-1344
10/2002
DOI: 10.1006/jmcc.2002.2085
PMID: 12392994
Abstract
B. D. Thattaliyath, B. A. Firulli and A. B. Firulli. The Basic-Helix-Loop-Helix Transcription Factor HAND2 Directly Regulates Transcription of the Atrial Naturetic Peptide Gene.Journal of Molecular and Cellular Cardiology (2002) 34, 1335–1344. The HAND basic Helix-Loop-Helix (bHLH) transcription factors are essential for the development of heart and extra embryonic structures. Although essential for embryonic development, the molecular pathways in which HAND factors participate are poorly understood. In efforts to identify downstream transcriptional targets, we have determined that HAND2 regulates the transcription of the Atrial Naturetic Peptide (ANP) gene. Results show that ANP expression is reduced in HAND2 null mice. Transactivation assays show significant transcriptional upregulation of ANP by HAND2 and cotransfection experiments using HAND2 and E12 suggest that an E-protein/HAND heterodimer is the likely trans -acting complex. The required cis -elements reside within a 258bp proximal region that contains three evolutionarily conserved Ebox consensus sites. Surprisingly, mutations in these three sites suggest HAND2 activity is DNA-binding independent. In addition, HAND2 and the homeobox factor Nkx2.5 exhibit transcriptional synergy in the regulation of ANP. Taken together, this data shows that HAND2 is an upstream transcriptional regulator of ANP expression, and furthermore HAND2 can synergistically interact with Nkx2.5, showing a functional relationship between HAND2 and Nkx2.5 supporting the genetic observation, that mice null for both HAND2 and Nkx2.5 lack ventricle specification.
Details
- Title: Subtitle
- The Basic-Helix-Loop-Helix Transcription Factor HAND2 Directly Regulates Transcription of the Atrial Naturetic Peptide Gene
- Creators
- Bijoy D ThattaliyathBeth A FirulliAnthony B Firulli
- Resource Type
- Journal article
- Publication Details
- Journal of molecular and cellular cardiology, Vol.34(10), pp.1335-1344
- Publisher
- Elsevier Ltd
- DOI
- 10.1006/jmcc.2002.2085
- PMID
- 12392994
- ISSN
- 0022-2828
- eISSN
- 1095-8584
- Language
- English
- Date published
- 10/2002
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics
- Record Identifier
- 9984093483502771
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