PT  - JOURNAL ARTICLE
AU  - Andrea Cirino
AU  - Ilaria Aurigemma
AU  - Monica Franzese
AU  - Gabriella Lania
AU  - Dario Righelli
AU  - Rosa Ferrentino
AU  - Elizabeth Illingworth
AU  - Claudia Angelini
AU  - Antonio Baldini
TI  - Chromatin and transcriptional response to loss of TBX1 in early differentiation of mouse cells
AID  - 10.1101/2020.06.06.137026
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.06.137026
4099  - http://biorxiv.org/content/early/2020/06/10/2020.06.06.137026.short
4100  - http://biorxiv.org/content/early/2020/06/10/2020.06.06.137026.full
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.