Histone H2A.X phosphorylation and Caspase-Initiated Chromatin Condensation in late-stage erythropoiesis
Abstract Background 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...
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doaj-49df9d0502544e9f8af90c63844d0d032021-08-01T11:29:09ZengBMCEpigenetics & Chromatin1756-89352021-07-0114111510.1186/s13072-021-00408-5Histone H2A.X phosphorylation and Caspase-Initiated Chromatin Condensation in late-stage erythropoiesisNazish N. Jeffery0Christina Davidson1Scott A. Peslak2Paul D. Kingsley3Yukio Nakamura4James Palis5Michael Bulger6Center for Pediatric Biomedical Research, Department of Pediatrics, University of RochesterWilmot Cancer Institute, Department of Biomedical Genetics, University of RochesterDepartment of Medicine, Division of Hematology/Oncology, Hospital of the University of PennsylvaniaCenter for Pediatric Biomedical Research, Department of Pediatrics, University of RochesterCell Engineering Division, RIKEN BioResource CenterCenter for Pediatric Biomedical Research, Department of Pediatrics, University of RochesterCenter for Pediatric Biomedical Research, Department of Pediatrics, University of RochesterAbstract Background 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 describe a potential role for the histone variant H2A.X in erythropoiesis. Results We 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. Conclusions We 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.https://doi.org/10.1186/s13072-021-00408-5H2A.Xg-H2A.XBAZ1BWSTFChromatin condensationErythropoiesis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nazish N. Jeffery Christina Davidson Scott A. Peslak Paul D. Kingsley Yukio Nakamura James Palis Michael Bulger |
spellingShingle |
Nazish N. Jeffery Christina Davidson Scott A. Peslak Paul D. Kingsley Yukio Nakamura James Palis Michael Bulger Histone H2A.X phosphorylation and Caspase-Initiated Chromatin Condensation in late-stage erythropoiesis Epigenetics & Chromatin H2A.X g-H2A.X BAZ1B WSTF Chromatin condensation Erythropoiesis |
author_facet |
Nazish N. Jeffery Christina Davidson Scott A. Peslak Paul D. Kingsley Yukio Nakamura James Palis Michael Bulger |
author_sort |
Nazish N. Jeffery |
title |
Histone H2A.X phosphorylation and Caspase-Initiated Chromatin Condensation in late-stage erythropoiesis |
title_short |
Histone H2A.X phosphorylation and Caspase-Initiated Chromatin Condensation in late-stage erythropoiesis |
title_full |
Histone H2A.X phosphorylation and Caspase-Initiated Chromatin Condensation in late-stage erythropoiesis |
title_fullStr |
Histone H2A.X phosphorylation and Caspase-Initiated Chromatin Condensation in late-stage erythropoiesis |
title_full_unstemmed |
Histone H2A.X phosphorylation and Caspase-Initiated Chromatin Condensation in late-stage erythropoiesis |
title_sort |
histone h2a.x phosphorylation and caspase-initiated chromatin condensation in late-stage erythropoiesis |
publisher |
BMC |
series |
Epigenetics & Chromatin |
issn |
1756-8935 |
publishDate |
2021-07-01 |
description |
Abstract Background 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 describe a potential role for the histone variant H2A.X in erythropoiesis. Results We 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. Conclusions We 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. |
topic |
H2A.X g-H2A.X BAZ1B WSTF Chromatin condensation Erythropoiesis |
url |
https://doi.org/10.1186/s13072-021-00408-5 |
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