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. Author manuscript; available in PMC: 2022 May 6.
Published in final edited form as: Mol Cell. 2021 Mar 15;81(9):1970–1987.e9. doi: 10.1016/j.molcel.2021.02.031

Fig.2: Polycomb loops protect against gene dysregulation upon cohesin loss, but increase sensitivity to cohesin gain during differentiation.

Fig.2:

(A) Genes upregulated or downregulated after indicated time courses of RAD21 degradation (relative to DMSO control) overlapping with H3K27me3 cChIP-seq peaks. All genes shown for reference.

(B) RAD21-FKBPdegron RNA-seq (day 7: PRO-seq) DESeq2 log2-fold (dTAG-13/DMSO) change (left) or log2 FPKM (day 7: FPK, right, averaged between clones) of different categories of expressed (day 7: all) H3K27me3-marked genes. (No) loop: (not) overlapping anchor of H3K27me3-associated, cohesin-independent loop, Hox: Hox gene located in Hox cluster. All genes shown for reference. Significant p-values by Wilcoxon rank test indicated by * (p<7.344e-05), ** (p<0.0006566), *** (p<2.847e-05), **** (p<0.0005113), ***** (p<0.003082), ****** (p<0.0006716), ******* (p<0.001102), ********* (p<0.000146). N.S., not significant.

(C) Average DMSO and dTAG-13 H3K27me3 cChIP-seq signal over upregulated and downregulated genes in day 7 RAD21-FKBPdegron and WAPL-FKBPdegron samples.

(D) Inter-chromosomal Hi-C interaction maps between Hox cluster regions in RAD21-FKBPdegron lines at day 7 and day 10 at indicated resolutions (clones merged). H3K27me3 cChIP-seq signal in day 7 RAD21- FKBPdegron lines shown for reference (scale: 200).

(E) Schematic of inter-chromosomal Hox interactions in mESCs, day 7 and day 10 of differentiation. Bold arrows, interactions detected by Hi-C under control conditions.

(F) Genes upregulated or downregulated upon WAPL degradation from days 7–10 (relative to DMSO control) overlapping with H3K27me3 cChIP-seq peaks. All genes shown for reference.

(G) WAPL-FKBPdegron RNA-seq log2-fold (dTAG-13/DMSO) change of different categories of expressed H3K27me3-marked genes in WAPL-FKBPdegron lines. Categories as in (B). Significant p-values by Wilcoxon rank test indicated by * (p<6.703e-08), ** (p<1.462e-07), *** (p<4.638e-05).

(H) Inter-chromosomal Hi-C interaction maps between Hox cluster regions in WAPL-FKBPdegron lines (clones merged) at indicated resolutions. H3K27me3 cChIP-seq signal in day 7 WAPL- FKBPdegron lines shown for reference (scale: 100).