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PITX2 isoform-specific regulation of atrial natriuretic factor expression - Synergism and repression with Nkx2.5

Ganga, M; Espinoza, HM; Cox, CJ; Morton, L; Hjalt, Tord LU ; Lee, Y and Amendt, BA (2003) In Journal of Biological Chemistry 278(25). p.22437-22445
Abstract
PITX2 and Nkx2.5 are two of the earliest known transcriptional markers of vertebrate heart development. Pitx2(-/-) mice present with severe cardiac malformations and embryonic lethality, demonstrating a role for PITX2 in heart development. However, little is known about the downstream targets of PITX2 in cardiogenesis. We report here that the atrial natriuretic factor ( ANF) promoter is a target of PITX2. PITX2A, PITX2B, and PITX2C isoforms differentially activate the ANF promoter. However, only PITX2C can synergistically activate the ANF promoter in the presence of Nkx2.5. We further demonstrate that the procollagen lysyl hydroxylase ( PLOD1) promoter is regulated by Nkx2.5. Mechanistically, PITX2C and Nkx2.5 synergistically regulate ANF... (More)
PITX2 and Nkx2.5 are two of the earliest known transcriptional markers of vertebrate heart development. Pitx2(-/-) mice present with severe cardiac malformations and embryonic lethality, demonstrating a role for PITX2 in heart development. However, little is known about the downstream targets of PITX2 in cardiogenesis. We report here that the atrial natriuretic factor ( ANF) promoter is a target of PITX2. PITX2A, PITX2B, and PITX2C isoforms differentially activate the ANF promoter. However, only PITX2C can synergistically activate the ANF promoter in the presence of Nkx2.5. We further demonstrate that the procollagen lysyl hydroxylase ( PLOD1) promoter is regulated by Nkx2.5. Mechanistically, PITX2C and Nkx2.5 synergistically regulate ANF and PLOD1 expression through binding to their respective DNA elements. Surprisingly, PITX2A activation of the ANF and PLOD1 promoters is repressed by co- transfection of Nkx2.5 in the C3H10T1/ 2 embryonic fibroblast cell line. Pitx2a and Pitx2c are endogenously expressed in C3H10T1/ 2 cells, and these cells express factors that differentially regulate PITX2 isoform activities. We provide a new mechanism for the regulation of heart development by PITX2 isoforms through the regulation of ANF and PLOD1 gene expression and Nkx2.5 transcriptional activity. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
278
issue
25
pages
22437 - 22445
publisher
ASBMB
external identifiers
  • wos:000183503900037
  • scopus:0038266156
ISSN
1083-351X
DOI
language
English
LU publication?
yes
id
8e9d1763-f7d6-4a01-9b4e-8e3bd91233f8 (old id 308524)
date added to LUP
2007-09-03 09:46:11
date last changed
2018-06-17 03:57:57
@article{8e9d1763-f7d6-4a01-9b4e-8e3bd91233f8,
  abstract     = {PITX2 and Nkx2.5 are two of the earliest known transcriptional markers of vertebrate heart development. Pitx2(-/-) mice present with severe cardiac malformations and embryonic lethality, demonstrating a role for PITX2 in heart development. However, little is known about the downstream targets of PITX2 in cardiogenesis. We report here that the atrial natriuretic factor ( ANF) promoter is a target of PITX2. PITX2A, PITX2B, and PITX2C isoforms differentially activate the ANF promoter. However, only PITX2C can synergistically activate the ANF promoter in the presence of Nkx2.5. We further demonstrate that the procollagen lysyl hydroxylase ( PLOD1) promoter is regulated by Nkx2.5. Mechanistically, PITX2C and Nkx2.5 synergistically regulate ANF and PLOD1 expression through binding to their respective DNA elements. Surprisingly, PITX2A activation of the ANF and PLOD1 promoters is repressed by co- transfection of Nkx2.5 in the C3H10T1/ 2 embryonic fibroblast cell line. Pitx2a and Pitx2c are endogenously expressed in C3H10T1/ 2 cells, and these cells express factors that differentially regulate PITX2 isoform activities. We provide a new mechanism for the regulation of heart development by PITX2 isoforms through the regulation of ANF and PLOD1 gene expression and Nkx2.5 transcriptional activity.},
  author       = {Ganga, M and Espinoza, HM and Cox, CJ and Morton, L and Hjalt, Tord and Lee, Y and Amendt, BA},
  issn         = {1083-351X},
  language     = {eng},
  number       = {25},
  pages        = {22437--22445},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {PITX2 isoform-specific regulation of atrial natriuretic factor expression - Synergism and repression with Nkx2.5},
  url          = {http://dx.doi.org/},
  volume       = {278},
  year         = {2003},
}