NOTCH1/RBPJ complexes drive target gene expression through dynamic interactions with super-enhancers

ABSTRACT: The main oncogenic driver in T-lymphoblastic leukemia (T-LL) is NOTCH1, which activates genes by forming chromatin-associated Notch transcription complexes. Gamma-secretase (GSI) inhibitor treatment prevents NOTCH1 nuclear localization, but most genes with NOTCH1 binding sites are insensitive to GSI. Here, we demonstrate that fewer than 10% of NOTCH1 binding sites show dynamic changes in NOTCH1 occupancy when T-LL cells are toggled between the Notch-on and –off states with GSI. Dynamic NOTCH1 sites are functional, being highly associated with Notch target genes, are located mainly in distal enhancers, and frequently overlap with RUNX1 binding. In line with the latter association, we show that expression of IL7R, a gene with key roles in normal T cell development and in T-LL, is coordinatel

ORGANISM(S): Homo sapiens

SUBMITTER: Chongzhi Zang 

PROVIDER: E-GEOD-51800 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress