RT Journal Article
SR Electronic
T1 Chromatin and transcriptional response to loss of TBX1 in early differentiation of mouse cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.06.137026
DO 10.1101/2020.06.06.137026
A1 Andrea Cirino
A1 Ilaria Aurigemma
A1 Monica Franzese
A1 Gabriella Lania
A1 Dario Righelli
A1 Rosa Ferrentino
A1 Elizabeth Illingworth
A1 Claudia Angelini
A1 Antonio Baldini
YR 2020
UL http://biorxiv.org/content/early/2020/06/10/2020.06.06.137026.abstract
AB The T-box transcription factor TBX1 has critical roles in the cardiopharyngeal lineage and the gene is haploinsufficient in DiGeorge syndrome, a typical developmental anomaly of the pharyngeal apparatus. Despite almost two decades of research, if and how TBX1 function triggers chromatin remodeling is not known.Here, we explored genome-wide gene expression and chromatin remodeling in two independent cellular models of Tbx1 loss of function, mouse embryonic carcinoma cells P19Cl6, and mouse embryonic stem cells (mESCs). The results of our study revealed that the loss or knockdown of TBX1 caused extensive transcriptional changes, some of which were cell type-specific, some were in common between the two models. However, unexpectedly we observed only limited chromatin changes in both systems. In P19Cl6 cells, differentially accessible regions (DARs) were not enriched in T-BOX binding motifs; in contrast, in mESCs, 34% (n=47) of all DARs included a T-BOX binding motif and almost all of them gained accessibility in Tbx1-/- cells.In conclusion, despite a clear transcriptional response of our cell models to loss of TBX1 in early cell differentiation, chromatin changes were relatively modest.Competing Interest StatementThe authors have declared no competing interest.