- Mechanisms of GATA factor-mediated regulation of molecular homeostasis in the gut
- Award date
- 13 February 2015
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
In this thesis, we determined the role of GATA factors in transcriptional regulation of intestinal genes, which ultimately forms the molecular basis of the complex physiology of the gut. The overall aim of this thesis is to determine GATA6 function in vivo and to delineate mechanisms of GATA4 activation and repression of absorptive enterocyte genes. We demonstrate a new GATA4/GATA6 redundant pathway that regulates proliferation, differentiation and absorptive enterocyte gene expression in the small intestine of which the proliferation function is mediated downstream through SPDEF. In colon, GATA6 regulates proliferation, migration, secretory cell maturation and colonocyte gene expression. We show that CDX2 and GATA4 are functionally redundant in promoting proliferation and that CDX2 partners with HNF1A and HNF4A to promote differentiation. Last, we show that GATA4 represses ileal genes in jejunum by inhibiting acetylation on histone H3K27. Overall, this thesis defines novel functions for GATA factors in the gut and adds new insights to a framework for how transcription factors in the gut may work together to establish certain cellular processes.
- Research conducted at: Universiteit van Amsterdam
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