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Differential regulation of gene expression by PITX2 isoforms

Cox, Carol J; Espinoza, Herbert M; McWilliams, Bryan; Chappell, Kimberly; Morton, Lisa; Hjalt, Tord LU ; Semina, Elena V and Amendt, Brad A (2002) In Journal of Biological Chemistry 277(28). p.25001-25010
Abstract
Three major PITX2 isoforms are differentially expressed in human, mice, zebrafish, chick, and frog tissues. To demonstrate differential regulation of gene expression by these isoforms we used three different promoters and three cell lines. Transient transfection of Chinese hamster ovary, HeLa, and LS-8 cell lines revealed differences in PITX2A and PITX2C activation of the PLOD1 and Dlx2 promoters, however, PITX2B is inactive. In contrast, PITX2B actives the pituitary-specific Prolactin promoter at higher levels than either PITX2A or PITX2C. Interestingly, co-transfection of either PITX2A or PITX2C with PITX2B results in a synergistic activation of the PLOD1 and Dlx2 promoters. Furthermore, PITX2 isoforms have different transcriptional... (More)
Three major PITX2 isoforms are differentially expressed in human, mice, zebrafish, chick, and frog tissues. To demonstrate differential regulation of gene expression by these isoforms we used three different promoters and three cell lines. Transient transfection of Chinese hamster ovary, HeLa, and LS-8 cell lines revealed differences in PITX2A and PITX2C activation of the PLOD1 and Dlx2 promoters, however, PITX2B is inactive. In contrast, PITX2B actives the pituitary-specific Prolactin promoter at higher levels than either PITX2A or PITX2C. Interestingly, co-transfection of either PITX2A or PITX2C with PITX2B results in a synergistic activation of the PLOD1 and Dlx2 promoters. Furthermore, PITX2 isoforms have different transcriptional activity dependent upon the cells used for transfection analysis. We have isolated a fourth PITX2 isoform (PITX2D) expressed only in humans, which acts to suppress the transcriptional activity of the other PITX2 isoforms. Electrophoretic mobility shift assays and glutathione S-transferase pull-down experiments demonstrated that all isoforms interact with PITX2D and that PITX2B forms heterodimeric complexes with PITX2A and PITX2C. Our research provides a molecular basis for differential gene regulation through the expression of PITX2 isoforms. PITX2 isoform activities are both promoter- and cell-specific, and our data reveal new mechanisms for PITX2-regulated gene expression. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
277
issue
28
pages
25001 - 25010
publisher
ASBMB
external identifiers
  • pmid:11948188
  • scopus:0037067729
ISSN
1083-351X
DOI
10.1074/jbc.M201737200
language
English
LU publication?
no
id
18d4a6b4-84ab-43c2-a237-9223a2b44ef7 (old id 1123938)
date added to LUP
2008-05-20 13:40:31
date last changed
2017-08-13 03:44:54
@article{18d4a6b4-84ab-43c2-a237-9223a2b44ef7,
  abstract     = {Three major PITX2 isoforms are differentially expressed in human, mice, zebrafish, chick, and frog tissues. To demonstrate differential regulation of gene expression by these isoforms we used three different promoters and three cell lines. Transient transfection of Chinese hamster ovary, HeLa, and LS-8 cell lines revealed differences in PITX2A and PITX2C activation of the PLOD1 and Dlx2 promoters, however, PITX2B is inactive. In contrast, PITX2B actives the pituitary-specific Prolactin promoter at higher levels than either PITX2A or PITX2C. Interestingly, co-transfection of either PITX2A or PITX2C with PITX2B results in a synergistic activation of the PLOD1 and Dlx2 promoters. Furthermore, PITX2 isoforms have different transcriptional activity dependent upon the cells used for transfection analysis. We have isolated a fourth PITX2 isoform (PITX2D) expressed only in humans, which acts to suppress the transcriptional activity of the other PITX2 isoforms. Electrophoretic mobility shift assays and glutathione S-transferase pull-down experiments demonstrated that all isoforms interact with PITX2D and that PITX2B forms heterodimeric complexes with PITX2A and PITX2C. Our research provides a molecular basis for differential gene regulation through the expression of PITX2 isoforms. PITX2 isoform activities are both promoter- and cell-specific, and our data reveal new mechanisms for PITX2-regulated gene expression.},
  author       = {Cox, Carol J and Espinoza, Herbert M and McWilliams, Bryan and Chappell, Kimberly and Morton, Lisa and Hjalt, Tord and Semina, Elena V and Amendt, Brad A},
  issn         = {1083-351X},
  language     = {eng},
  number       = {28},
  pages        = {25001--25010},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Differential regulation of gene expression by PITX2 isoforms},
  url          = {http://dx.doi.org/10.1074/jbc.M201737200},
  volume       = {277},
  year         = {2002},
}