Dynamic Runx1 chromatin boundaries affect gene expression in hematopoietic development

• DOI: 10.1038/s41467-022-28376-8
• Publication Date: 2022-02-09T11:04:57Z
• Authors: Dominic D. G. Owens; Giorgio Anselmi; A. Marieke Oudelaar; Damien J. Downes; Alessandro Cavallo; Joe R. Harman; Ron Schwessinger; Akin Bucakci; Lucas Greder; Sara de Ornellas; Danuta Jeziorska; Jelena Telenius; Jim R. Hughes; Marella F. T. R. ...
• Keywords: RUNX1; CTCF

Abstract The transcription factor RUNX1 is a critical regulator of developmental hematopoiesis and frequently disrupted in leukemia. Runx1 large, complex gene that expressed from two alternative promoters under the spatiotemporal control multiple hematopoietic enhancers. To dissect dynamic regulation development, we analyzed its three-dimensional chromatin conformation mouse embryonic stem cell (ESC) differentiation cultures. resides 1.1 Mb topologically associating domain (TAD) demarcated by convergent CTCF motifs. As ESCs differentiate to mesoderm, accessibility, enhancer-promoter (E-P) interactions, CTCF-CTCF interactions increase TAD, along with initiation expression P2 promoter. Differentiation progenitor cells associated formation tissue-specific sub-TADs over , shift E-P P1 promoter demethylation, robust both promoters. Deletion promoter-proximal sites at sub-TAD boundaries has no obvious effects on but leads partial loss structure, mildly affects expression, delays development. Together, our analysis large multi-promoter reveals play role establishing TAD structure coordinated expression.