cooperation of p300 and pcaf in the control of microrna 200c141 transcription and epithelial characteristics合作的p300和pcaf microrna 200 c141转录和上皮的控制特点.pdf

Cooperation of p300 and PCAF in the Control of MicroRNA 200c/141 Transcription and Epithelial Characteristics Yoshiaki Mizuguchi1,2, Susan Specht1,2, John G. Lunz III1,2,3, Kumiko Isse1,2, Natasha Corbitt1,2, Toshihiro Takizawa4, Anthony J. Demetris1,2* 1Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America, 2 Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America, 3 Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America, 4 Department of Molecular Anatomy and Medicine, Nippon Medical School, Tokyo, Japan Abstract Epithelial to mesenchymal transition (EMT) not only occurs during embryonic development and in response to injury, but is an important element in cancer progression. EMT and its reverse process, mesenchymal to epithelial transition (MET) is controlled by a network of transcriptional regulators and can be influenced by posttranscriptional and posttranslational modifications. EMT/MET involves many effectors that can activate and repress these transitions, often yielding a spectrum of cell phenotypes. Recent studies have shown that the miR-200 family and the transcriptional suppressor ZEB1 are important contributors to EMT. Our previous data showed that forced expression of SPRR2a was a powerful inducer of EMT and supports the findings by others that SPRR gene members are highly upregulated during epithelial remodeling in a variety of organs. Here, using SPRR2a cells, we characterize the role of acetyltransferases on the microRNA-200c/141 promoter and their effect on the epithelial/mesenchymal status of the cells. We show that the deacetylase inhibitor TSA as well as P300 and PCAF can cause a shift towards epithelial chara