PT  - JOURNAL ARTICLE
AU  - Timothy A Blenkinsop
AU  - Tomasz Swigut
AU  - Nathan Boles
AU  - Rajini Srinivasan
AU  - Alvaro Rada-Iglesias
AU  - Qingjie Wang
AU  - Jeffrey H Stern
AU  - Joanna Wysocka
AU  - Sally Temple
TI  - <em>FOXS1</em> is a Master Regulator of Pathological Epithelial to Mesenchymal Transition in Human Epithelia
AID  - 10.1101/154369
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 154369
4099  - http://biorxiv.org/content/early/2017/06/26/154369.short
4100  - http://biorxiv.org/content/early/2017/06/26/154369.full
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.