Wnt/β-catenin activation epigenetically reprograms Regulatory T cells in IBD and progression to dysplasia

Previous work indicated that β-catenin/TCF-1 occupy DNA together with Foxp3. Thus, we anticipated that precise mapping of TCF-1 and Foxp3 co-binding in Tregs, could provide a molecular explanation for our phenotypic observations. To address this, we analyzed TCF-1 DNA binding in Tregs through chromatin immunoprecipitation and deep sequencing (ChIPseq) in Foxp3YFP-Cre WT Tregs. Furthermore, we assessed regions of accessible chromatin in Tregs via transposase-accessible chromatin approach and deep sequencing (ATAC-seq). We also performed RNA-seq expression profiling to investigate how the changes in chromatin accessibility impacted transcription in β-catenin high Tregs. mRNA profiles and ATACseq derived from of 21-day old Foxp3Cre-YFP (WT) and Foxp3Cre-YFP Ctnnb1flex3 (CAT) male mice were generated by deep sequencing, in triplicate, using Illumina