Fig. 10: HDAC1/2 interact with SATB2 more strongly in MTA2^cKO vs. control colonoids, and HDAC activity is required for small intestine gene activation in MTA2^cKO colon.

a immunoblots and quantification of SATB2 and core NuRD subunits showed a slight decrease of HDAC2, but no change in HDAC1 or CHD4 in MTA2^cKO vs. control colonoids. Mean ± S.D. n = 3 independent samples. P value by unpaired t test with Welch correction, adjusted by FDR (1%). All the different gels/blots were derived from the same experiment and were processed in parallel. b Co-IP and quantification showed stronger interaction of HDAC1/2 with SATB2, but not CHD4 with SATB2 in MTA2^cKO vs. control colonoids. Mean ± S.D. n = 3 independent samples. P value by unpaired t-test with Welch correction, adjusted by FDR (1%). All the different gels/blots were derived from the same experiment and were processed in parallel. c QPCR showed treatment with the HDAC inhibitors 4PBA and SAHA attenuated small intestine gene activation in MTA2^cKO organoids. Mean ± S.D. n = 3. P value by Unpaired t-test. d A proposed model of colonocyte plasticity regulation in which MTA2 and SATB2 form a chromatin complex at colonic chromatin to retain HNF4A. SATB2 restrains HNF4A more tightly than MTA2. MTA2 loss leads to a modest depletion of HNF4A on colonic and gain on small intestine (SI) chromatin, and modest down- and up-regulation of colonic and small intestine (SI) genes. In contrast, SATB2 loss results in the untethering of large numbers of HNF4A and consequently transcriptomic shift from colon to small intestine. Yellow bar denotes primed small intestinal enhancers in colon.