Histone H2A.X phosphorylation and Caspase-Initiated Chromatin Condensation in late-stage erythropoiesis

Epigenetics & Chromatin

Yukio Nakamura¹  Paul D. Kingsley²  James Palis²  Michael Bulger²  Nazish N. Jeffery²  Scott A. Peslak³  Christina Davidson⁴ 

[1] Cell Engineering Division, RIKEN BioResource Center, Tsukuba, Ibaraki, Japan;Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester, Rochester, NY, USA;Department of Medicine, Division of Hematology/Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA;Division of Hematology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA;Wilmot Cancer Institute, Department of Biomedical Genetics, University of Rochester, Rochester, NY, USA;

关键词: H2A.X;    g-H2A.X;    BAZ1B;    WSTF;    Chromatin condensation;    Erythropoiesis;    Terminal erythroid maturation;    Caspase;    Phosphorylation;    Apoptosis;   

DOI  :  10.1186/s13072-021-00408-5

来源: Springer

【 摘 要 】

BackgroundCondensation 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 describe a potential role for the histone variant H2A.X in erythropoiesis.ResultsWe find in multiple model systems that this histone is essential for normal maturation, and that the loss of H2A.X in erythroid cells results in dysregulation in expression of erythroid-specific genes as well as a nuclear condensation defect. In addition, we demonstrate that erythroid maturation is characterized by phosphorylation at both S139 and Y142 on the C-terminal tail of H2A.X during late-stage erythropoiesis. Knockout of the kinase BAZ1B/WSTF results in loss of Y142 phosphorylation and a defect in nuclear condensation, but does not replicate extensive transcriptional changes to erythroid-specific genes observed in the absence of H2A.X.ConclusionsWe relate these findings to Caspase-Initiated Chromatin Condensation (CICC) in terminal erythroid maturation, where aspects of the apoptotic pathway are invoked while apoptosis is specifically suppressed.

【 授权许可】

CC BY