TY - JOUR T1 - KLF4 Recruits SWI/SNF to Increase Chromatin Accessibility and Reprogram the Endothelial Enhancer Landscape under Laminar Shear Stress JF - bioRxiv DO - 10.1101/2020.07.10.195768 SP - 2020.07.10.195768 AU - Jan-Renier A.J. Moonen AU - James Chappell AU - Minyi Shi AU - Tsutomu Shinohara AU - Dan Li AU - Maxwell R. Mumbach AU - Fan Zhang AU - Joseph Nasser AU - Daniel H. Mai AU - Shalina Taylor AU - Lingli Wang AU - Ross J. Metzger AU - Howard Y. Chang AU - Jesse M. Engreitz AU - Michael P. Snyder AU - Marlene Rabinovitch Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/07/10/2020.07.10.195768.abstract N2 - Physiologic laminar shear stress (LSS) induces an endothelial gene expression profile that is vasculo-protective. In this report, we delineate how LSS mediates changes in the epigenetic landscape to promote this beneficial response. We show that under LSS, KLF4 interacts with the SWI/SNF nucleosome remodeling complex to increase accessibility at enhancer sites that promote expression of homeostatic endothelial genes. By combining molecular and computational approaches we discovered enhancers that loop to promoters of known and novel KLF4- and LSS-responsive genes that stabilize endothelial cells and suppress inflammation, such as BMPR2 and DUSP5. By linking enhancers to genes that they regulate under physiologic LSS, our work establishes a foundation for interpreting how non-coding DNA variants in these regions might disrupt protective gene expression to influence vascular disease.Competing Interest StatementThe authors have declared no competing interest. ER -