These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: NFAT directly regulates Nkx2-5 transcription during cardiac cell differentiation.
    Author: Chen Y, Cao X.
    Journal: Biol Cell; 2009 Jun; 101(6):335-49. PubMed ID: 18828760.
    Abstract:
    BACKGROUND INFORMATION: The transcription factor NFAT (nuclear factor of activated T-cell) family comprises important regulators in immuno-responses and mouse embryonic development, including early cardiovascular and heart valve development. The mechanism involved, however, is not fully understood. Nkx2-5 (NK2 transcription factor related, locus 5) is one of the earliest genes expressed in early cardiac progenitor cells and is essential for heart tube development by control of a subset of cardiac muscle-specific genes. Previously we found that downregulation of mitochondrial respiratory chain complex I caused severe cardiac deficiencies during heart tube development in Xenopus embryos associated with compromised Nkx2-5 expression. However, the heart defects and Nkx2-5 expression could be rescued by a constitutively activated NFAT, suggesting a possible link between NFAT and Nkx2-5 during early heart development. RESULTS: In the present study, we demonstrate that NFAT regulates Nkx2-5 expression in both mouse ES (embryonic stem) cells and P19 cells, a mouse model for embryonic differentiation. We found that there are six core NFAT-binding elements in the 5' regulatory region of the Nkx2-5 gene. Although NFAT is able to bind directly to all but one of these elements, it activates Nkx2-5 transcription only via a specific binding site in the distal enhancer region. Interestingly, the transcriptional activity of NFAT is largely dependent on the co-factor GATA (GATA-binding transcription factor), which binds to an element adjacent to this key NFAT-binding site. Furthermore, binding of the endogenous NFAT to this particular site was observed during cardiac differentiation in mouse ES and P19 cells. CONCLUSIONS: The results suggest that Nkx2-5 is a direct target of NFAT that co-ordinates with other transcription factors such as GATA4 to regulate Nkx2-5 during cardiogenesis.
    [Abstract] [Full Text] [Related] [New Search]