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The histone H3.3 chaperone HIRA restrains erythroid-biased differentiation of adult hematopoietic stem cells
- Source :
- Stem Cell Reports
- Publication Year :
- 2021
- Publisher :
- Elsevier, 2021.
-
Abstract
- Summary Histone variants contribute to the complexity of the chromatin landscape and play an integral role in defining DNA domains and regulating gene expression. The histone H3 variant H3.3 is incorporated into genic elements independent of DNA replication by its chaperone HIRA. Here we demonstrate that Hira is required for the self-renewal of adult hematopoietic stem cells (HSCs) and to restrain erythroid differentiation. Deletion of Hira led to rapid depletion of HSCs while differentiated hematopoietic cells remained largely unaffected. Depletion of HSCs after Hira deletion was accompanied by increased expression of bivalent and erythroid genes, which was exacerbated upon cell division and paralleled increased erythroid differentiation. Assessing H3.3 occupancy identified a subset of polycomb-repressed chromatin in HSCs that depends on HIRA to maintain the inaccessible, H3.3-occupied state for gene repression. HIRA-dependent H3.3 incorporation thus defines distinct repressive chromatin that represses erythroid differentiation of HSCs.<br />Graphical abstract<br />Highlights • Deletion of Hira depletes adult HSCs but not fetal liver HSCs • HIRA represses hematopoietic development and erythropoiesis genes in HSCs • Cell division exacerbates gene derepression in Hira-deficient HSCs • H3.3 deposition and the closed state of polycomb-repressed chromatin depend on HIRA<br />Murdaugh et al. demonstrate that deletion of the histone H3.3 chaperone Hira depletes adult but not fetal liver HSCs by inducing differentiation. Hira regulates H3.3 deposition at a subset of polycomb-repressed chromatin that encodes genes involved in hematopoietic development, which becomes accessible and derepressed in the absence of Hira.
- Subjects :
- Cell division
Cell Cycle Proteins
Mice, Transgenic
Biology
Biochemistry
histone H3.3
Article
Histones
Histone H3
Erythroid Cells
Gene expression
Genetics
medicine
Animals
Histone Chaperones
Epigenetics
RNA-Seq
Cell Self Renewal
Mice, Knockout
epigenetics
Gene Expression Profiling
Age Factors
Hematopoietic stem cell
Cell Differentiation
Cell Biology
differentiation
Hematopoietic Stem Cells
Hira
hematopoiesis
Chromatin
Cell biology
Mice, Inbred C57BL
Haematopoiesis
Adult Stem Cells
medicine.anatomical_structure
Gene Ontology
Animals, Newborn
hematopoietic stem cell
Stem cell
polycomb
erythropoiesis
Developmental Biology
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 22136711
- Volume :
- 16
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Stem Cell Reports
- Accession number :
- edsair.doi.dedup.....bd959fec037219c8bbe1ff022ae917e8