Genome-wide chromatin maps of T-cell acute lymphoblastic leukemia (T-ALL) [ChIP-seq]

ABSTRACT: Here we modeled T-ALL resistance to Notch inhibition, identifying M-bM-^@M-^XpersisterM-bM-^@M-^Y cells that readily expand in the presence of gamma secretase inhibitor (GSI) and the absence of Notch signaling. Rare persister cells are already present in naM-CM-/ve T-ALL populations, and the reversibility of the phenotype is suggestive of an epigenetic mechanism. Relative to GSI-sensitive cells, persisters activate distinct signaling and gene expression programs, and exhibit global chromatin compaction. A shRNA screen identified chromatin regulators whose depletion preferentially impairs persister cell viability, including BRD4, an acetyl-histone reader. BRD4 is up-regulated in the persisters and binds enhancers near genes with critical functions in T-ALL, including MYC and BCL2. Treatment

ORGANISM(S): Homo sapiens

SUBMITTER: Jiang Zhu 

PROVIDER: E-GEOD-54379 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress