The T-box transcription factor TBX1 has critical roles in the cardiopharyngeal lineage and 82 the gene is haploinsufficient in DiGeorge syndrome, a typical developmental anomaly of 83 the pharyngeal apparatus. Despite almost two decades of research, if and how TBX1 84 function triggers chromatin remodeling is not known. Here, we explored genome-wide 85 gene expression and chromatin remodeling in two independent cellular models of Tbx1 86 87 loss of function, mouse embryonic carcinoma cells P19Cl6, and mouse embryonic stem 88 cells (mESCs). The results of our study revealed that the loss or knockdown of TBX1 89 caused extensive transcriptional changes, some of which were cell type-specific, some 90 were in common between the two models. However, unexpectedly we observed only 91 limited chromatin changes in both systems. In P19Cl6 cells, differentially accessible 92 93 regions (DARs) were not enriched in T-BOX binding motifs; in contrast, in mESCs, 34% 94 (n = 47) of all DARs included a T-BOX binding motif and almost all of them gained 95 accessibility in Tbx1− / − cells. In conclusion, despite a clear transcriptional response 96 of our cell models to loss of TBX1 in early cell differentiation, chromatin changes were 97 98 relatively modest.
Chromatin and Transcriptional Response to Loss of TBX1 in Early Differentiation of Mouse Cells
Aurigemma, Ilaria;Righelli, Dario;Illingworth, Elizabeth;Angelini, Claudia
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2020-01-01
Abstract
The T-box transcription factor TBX1 has critical roles in the cardiopharyngeal lineage and 82 the gene is haploinsufficient in DiGeorge syndrome, a typical developmental anomaly of 83 the pharyngeal apparatus. Despite almost two decades of research, if and how TBX1 84 function triggers chromatin remodeling is not known. Here, we explored genome-wide 85 gene expression and chromatin remodeling in two independent cellular models of Tbx1 86 87 loss of function, mouse embryonic carcinoma cells P19Cl6, and mouse embryonic stem 88 cells (mESCs). The results of our study revealed that the loss or knockdown of TBX1 89 caused extensive transcriptional changes, some of which were cell type-specific, some 90 were in common between the two models. However, unexpectedly we observed only 91 limited chromatin changes in both systems. In P19Cl6 cells, differentially accessible 92 93 regions (DARs) were not enriched in T-BOX binding motifs; in contrast, in mESCs, 34% 94 (n = 47) of all DARs included a T-BOX binding motif and almost all of them gained 95 accessibility in Tbx1− / − cells. In conclusion, despite a clear transcriptional response 96 of our cell models to loss of TBX1 in early cell differentiation, chromatin changes were 97 98 relatively modest.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
