Extended Data Fig. 10: Regulation of the Igh locus in pro-B cells and summary of interactions of E2A, Ebf1, Pax5, Ikaros, and Aiolos with relevant target genes.

a, Chromatin accessibility, nascent transcript abundance, and binding of Ebf1 (upper part) and Pax5 (lower part) at the Igh locus. TF binding was determined by CUT&RUN analysis in untreated pro-B cells, while nascent transcripts and open chromatin were determined by total RNA-seq and ATAC-seq, respectively, before (–) and after (+) 5-Ph-IAA treatment. Known regulatory elements are indicated. b, Schematic diagram depicting extended loop extrusion across the entire 2.8-Mb long Igh locus upon Pax5-mediated repression of the cohesin-release factor Wapl in pro-B cells⁴³. The cohesin complex (orange) generates chromatin loops by extruding DNA sequences at the Igh locus. The Rag1,2-bound recombination center (gray) is located at the DJ_H-rearranged gene segment in the 3′ proximal ___domain. Ongoing loop extrusion leads to convergent alignment of the 12-RSS (recognition signal sequence with a 12-bp spacer, black arrowhead) of the D_H segment and the 23-RSS (green arrowhead) of the V_H genes, which mediates RAG-cleavage and subsequent V_H-DJ_H joining. c, Summary of the interactions of E2A, Ebf1, Pax5, Ikaros, and Aiolos with relevant target genes described in this publication. Gene activation and repression is shown in blue and red, respectively. Interactions in pro-B, pre-B, and immature B cells are indicated by dotted, dashed and full lines, respectively. Interactions are shown for regulated target genes (>1.5-fold). The transcriptional data of the following target genes are shown in the indicated figures: Cd19 (Extended Data Fig. 5b), Bcl2l1, Ikzf1 (Fig. 3b, c), Bach2, Cbfa2t3, E2f2, Ebf1, Myb, Myc, Pax5, Pou2af1, Tcf3 (Fig. 6), Ikzf3 (Extended Data Fig. 4b), Dntt, Igll1, Irf4, Irf8, Rag1, Rag2 (Fig. 7), Vpreb1 (Extended Data Fig. 9c), and Wapl (Fig. 8a).