RT Journal Article SR Electronic T1 A histidine cluster determines YY1-compartmentalized coactivators and chromatin elements in phase-separated super-enhancers JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.09.15.460559 DO 10.1101/2021.09.15.460559 A1 Wenmeng Wang A1 Shiyao Qiao A1 Guangyue Li A1 Cuicui Yang A1 Chen Zhong A1 Daniel B. Stovall A1 Jinming Shi A1 Dangdang Li A1 Guangchao Sui YR 2021 UL http://biorxiv.org/content/early/2021/09/16/2021.09.15.460559.abstract AB As an oncogenic transcription factor, Yin Yang 1 (YY1) regulates enhancer and promoter connection. However, gaps still exist in understanding how YY1 coordinates coactivators and chromatin elements to assemble super-enhancers. Here, we demonstrate that YY1 activates FOXM1 gene expression through forming liquid-liquid phase separation to compartmentalize both coactivators and enhancer elements. In the transactivation domain of YY1, a histidine cluster is essential for its activities of forming phase separation, which can be extended to additional proteins. Coactivators EP300, BRD4, MED1 and active RNA polymerase II are components of YY1-rich nuclear puncta. Consistently, histone markers for gene activation, but not repression, colocalize with YY1. Importantly, multiple enhancer elements and the FOXM1 promoter are bridged by YY1 to form super-enhancers. These studies propose that YY1 is a general transcriptional activator, and promotes phase separation with incorporation of major coactivators and stabilization by distal enhancers to activate target gene expression.Competing Interest StatementThe authors have declared no competing interest.