RT Journal Article SR Electronic T1 FOXS1 is a Master Regulator of Pathological Epithelial to Mesenchymal Transition in Human Epithelia JF bioRxiv FD Cold Spring Harbor Laboratory SP 154369 DO 10.1101/154369 A1 Timothy A Blenkinsop A1 Tomasz Swigut A1 Nathan Boles A1 Rajini Srinivasan A1 Alvaro Rada-Iglesias A1 Qingjie Wang A1 Jeffrey H Stern A1 Joanna Wysocka A1 Sally Temple YR 2017 UL http://biorxiv.org/content/early/2017/06/26/154369.abstract AB Epithelial to mesenchymal transition (EMT) is a biological process involved in normal tissue morphogenesis and also in disease pathology. It causes dramatic alterations in cell morphology, migration, proliferation, and phenotype. We captured the global transcriptional and epigenetic programs elicited when polarized, cobblestone human retinal pigment epithelial (RPE) cells were stimulated to undergo EMT, a process associated with several retinal pathologies. The reorganization of chromatin landscapes occurred preferentially at distal enhancers, rather than promoter regions, accompanied by 3136 significantly changing genes. Of the 95 significantly changing transcription factors, FOXS1 was most upregulated. Loss and gain of function experiments demonstrated that FOXS1 is upstream of canonical EMT regulators, and can stimulate EMT in RPE and other epithelia. Inhibition of p38, stimulated by combined action of the EMT-inducing factors, TGFβ1 and TNFα, dampened FOXS1 expression. An increase of FOXS1 in several cancers indicates it has a role in several EMT-involved pathologies.