TCF7L2 silencing results in altered gene expression patterns accompanied by local genomic reorganization.

ABSTRACT: Canonical Wnt signaling is crucial for intestinal homeostasis as TCF4, the major Wnt signaling effector in the intestines, is required for stem cell maintenance. The capability of TCF4 to maintain the stem cell phenotype is contingent upon β-catenin, a potent transcriptional activator, which interacts with histone acetyltransferases and chromatin remodeling complexes. We used RNAi to explore the influence of TCF4 on chromatin structure (Hi-C) and gene expression (RNA sequencing) across a 72-hour time series in colon cancer. We found that TCF4 reduction results in a disproportionate up-regulation of gene expression, including a powerful induction of SOX2. Integration of RNA sequencing and Hi-C data revealed a TAD boundary loss, which occurred concomitantly with the over-expression of a clus

SUBMITTER: Brown MA 

PROVIDER: S-EPMC7809436 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature