Chromatin and transcriptional response to loss of TBX1 in early differentiation of mouse cells
The T-box transcription factor TBX1 has critical roles in the cardiopharyngeal lineage and the gene is haploinsufficient in DiGeorge syndrome, an archetypal developmental anomaly of the pharyngeal apparatus. Despite almost two decades of research, the mechanisms by which TBX1 interacts with chromatin and with chromatin remodeling complexes are not known in detail.Here, we explored genome-wide gene expression and chromatin remodeling in two independent cellular models of Tbx1 loss of function. The results of our study revealed that the loss or knock-down of TBX1 causes modest chromatin changes in both systems although there were extensive transcriptional changes. In one of the models, we compared a TBX1 localization map with chromatin accessibility and found that almost all the binding sites were in non-accessible regions, as measured by the ATAC-seq assay.Overall, our results indicated that in the two systems studied, loss of TBX1 in early cell differentiation causes significant gene expression changes but modest chromatin remodeling