The Znf711-Phf8 complex functions as a transcriptional rheostat essential for neutrophil development

In this study, we demonstrate that the zinc finger protein Znf711 and its interacting partner, the Phd finger protein Phf8, are critical for granulopoiesis. Notably, our mechanistic studies reveal that Znf711 and Phf8 no longer function synergistically as a well-characterized combination of transcriptional activator and coactivator during this process.

Instead, Znf711 regulates neutrophil maturation in a DNA-binding independent manner by preventing its partner Phf8 from binding to chromatin. Furthermore, rather than solely acting as a histone lysine demethylase that activates transcription, Phf8, when SUMOylated, also plays a key role as a corepressor of the transcription factor Gfi1aa to inhibit the expression of the master myeloid regulator c/ebpα. Additionally, we identify a positive feedback loop between c/ebpα and znf711, which ensures a high level of c/ebpα expression at the early stages of terminal granulopoiesis to promote cell differentiation.