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Histone H2A.X Phosphorylation Activates Caspase-Induced Chromatin Condensation in Late Stage Erythropoiesis

ABSTRACT: Condensation of chromatin prior to enucleation is an essential component of terminal erythroid maturation, and defects in this process are associated with inefficient erythropoiesis and anemia. However, the mechanisms involved in this phenomenon are not well understood. Here, we identify a novel role for the histone variant H2A.X in erythropoiesis. We find in multiple model systems that this histone is essential for normal maturation and the loss of H2A.X in erythroid cells results in dysregulation in expression of erythroid specific genes as well a nuclear condensation defect. In Addition, we demonstrate that erythroid maturation is characterized by phosphorylation at both S139 and Y142 during late stage erythropoiesis. Knockout of the kinase BAZ1B/WSTF results in loss of Y142 phosphorylation and similar to loss of H2A.X, a defect in nuclear condensation. In this study, we present a model in which post-translational modifications on histone H2A.X during terminal erythroid maturation leads to Caspase-Induced Chromatin Condensation (CICC). In this novel pathway, although apoptosis is specifically suppressed, aspects of the apoptotic pathway remain active to drive terminal erythroid maturation. Suggesting that terminal erythroid maturation is indeed is a unique form of apoptosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE159422 | GEO | 2021/08/03

REPOSITORIES: GEO

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