Loss of Kat2a enhances transcriptional noise and depletes acute myeloid leukemia stem-like cells.

ABSTRACT: Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy with abnormal progenitor self-renewal and defective white blood cell differentiation. Its pathogenesis comprises subversion of transcriptional regulation, through mutation and by hijacking normal chromatin regulation. Kat2a is a histone acetyltransferase central to promoter activity, that we recently associated with stability of pluripotency networks, and identified as a genetic vulnerability in AML. Through combined chromatin profiling and single-cell transcriptomics of a conditional knockout mouse, we demonstrate that Kat2a contributes to leukemia propagation through preservation of leukemia stem-like cells. Kat2a loss impacts transcription factor binding and reduces transcriptional burst frequency in a subset of gene

SUBMITTER: Domingues AF 

PROVIDER: S-EPMC7039681 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature