GATA2 deficiency elevates interferon regulatory factor-8 to subvert a progenitor cell differentiation program.

ABSTRACT: Cell type-specific transcription factors control stem and progenitor cell transitions by establishing networks containing hundreds of genes and proteins. Network complexity renders it challenging to discover essential versus modulatory or redundant components. This scenario is exemplified by GATA2 regulation of hematopoiesis during embryogenesis. Loss of a far upstream Gata2 enhancer (-77) disrupts the GATA2-dependent transcriptome governing hematopoietic progenitor cell differentiation. The aberrant transcriptome includes the transcription factor interferon regulatory factor 8 (IRF8) and a host of innate immune regulators. Mutant progenitors lose the capacity to balance production of diverse hematopoietic progeny. To elucidate mechanisms, we asked if IRF8 is essential, contributory, or no

SUBMITTER: Johnson KD 

PROVIDER: S-EPMC8905696 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature