Mitogen-activated protein kinase-mediated disruption of enhancer-promoter communication inhibits hepatocyte nuclear factor 4alpha expression. Export

@article{citeulike:2192640, abstract = {Hepatocyte nuclear factor 4 (HNF-4) is a key member of the transcription factor network regulating hepatocyte differentiation and function. Activation of the HNF-4 gene involves physical interaction between a distant enhancer and the proximal promoter region, bound by distinct sets of transcription factors. Here we report that, upon mitogen-activated protein (MAP) kinase activation, HNF-4 expression is downregulated in human hepatoma cells. This effect is mediated by the loss of CEBPalpha expression. During MAP kinase signaling, the recruitment of HNF-3beta and HNF-1alpha to the HNF-4 enhancer and RNA polymerase II to the proximal HNF-4 promoter was compromised. CBP, Brg1, and TFIIB were also dissociated from the HNF-4 regulatory regions, and the enhancer-promoter complex was disrupted. Interestingly, the extent of nucleosome acetylation did not decrease at either regulatory region, and HNF-6 and HNF-1alpha, as well as components of the TFIID, remained associated with the proximal promoter during the repressed state. The results point to an absolute requirement of enhancer-promoter communication for maintaining the active state of the HNF-4 gene and provide evidence for a molecular bookmarking mechanism, which may contribute to the prevention of permanent silencing of the locus during the repressed state.}, address = {Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Herakleion, Crete, Greece.}, author = {Hatzis, P. and Kyrmizi, I. and Talianidis, I.}, citeulike-article-id = {2192640}, citeulike-linkout-0 = {http://dx.doi.org/10.1128/MCB.00297-06}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16980607}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16980607}, doi = {10.1128/MCB.00297-06}, issn = {0270-7306}, journal = {Mol Cell Biol}, keywords = {hnf4, interaction, phosphorylation}, month = {October}, number = {19}, pages = {7017--7029}, posted-at = {2008-01-03 23:32:31}, priority = {2}, title = {Mitogen-activated protein kinase-mediated disruption of enhancer-promoter communication inhibits hepatocyte nuclear factor 4alpha expression.}, url = {http://dx.doi.org/10.1128/MCB.00297-06}, volume = {26}, year = {2006} }

TY - JOUR ID - citeulike:2192640 L3 - citeulike-article-id:2192640 N2 - Hepatocyte nuclear factor 4 (HNF-4) is a key member of the transcription factor network regulating hepatocyte differentiation and function. Activation of the HNF-4 gene involves physical interaction between a distant enhancer and the proximal promoter region, bound by distinct sets of transcription factors. Here we report that, upon mitogen-activated protein (MAP) kinase activation, HNF-4 expression is downregulated in human hepatoma cells. This effect is mediated by the loss of CEBPalpha expression. During MAP kinase signaling, the recruitment of HNF-3beta and HNF-1alpha to the HNF-4 enhancer and RNA polymerase II to the proximal HNF-4 promoter was compromised. CBP, Brg1, and TFIIB were also dissociated from the HNF-4 regulatory regions, and the enhancer-promoter complex was disrupted. Interestingly, the extent of nucleosome acetylation did not decrease at either regulatory region, and HNF-6 and HNF-1alpha, as well as components of the TFIID, remained associated with the proximal promoter during the repressed state. The results point to an absolute requirement of enhancer-promoter communication for maintaining the active state of the HNF-4 gene and provide evidence for a molecular bookmarking mechanism, which may contribute to the prevention of permanent silencing of the locus during the repressed state. IS - 19 JF - Mol Cell Biol SN - 0270-7306 AD - Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Herakleion, Crete, Greece. EP - 7029 TI - Mitogen-activated protein kinase-mediated disruption of enhancer-promoter communication inhibits hepatocyte nuclear factor 4alpha expression. VL - 26 SP - 7017 KW - hnf4 KW - interaction KW - phosphorylation AU - Hatzis, P AU - Kyrmizi, I AU - Talianidis, I PY - 2006/10// UR - http://dx.doi.org/10.1128/MCB.00297-06 ER -