HIRA, a DiGeorge Syndrome Candidate Gene, Confers Proper Chromatin Accessibility on HSCs and Supports All Stages of Hematopoiesis

Chen, C.; Sun, Miao‐Kun; Warzecha, Claude C.; Bachu, Mahesh; Dey, Anup; Wu, Tsung‐Tsong; Adams, Peter D.; Macfarlan, Todd S.; Love, Paul E.; Ozato, Keiko

doi:10.1016/j.celrep.2020.01.062

Cited by 18 publications

(19 citation statements)

References 69 publications

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“…A recent paper showed that Hira loss underlies immune cell deficiencies in DiGeorge syndrome patients by impairing HSPC differentiation ( Chen et al., 2020 ). Consistently, our HSC transplantation assays showed that Hira deletion severely compromised myeloid and lymphoid lineage reconstitution.…”

Section: Discussionmentioning

confidence: 99%

The histone H3.3 chaperone HIRA restrains erythroid-biased differentiation of adult hematopoietic stem cells

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

The histone H3.3 chaperone HIRA restrains erythroid-biased differentiation of adult hematopoietic stem cells

et al. 2021

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“…Histone chaperones fulfill pivotal roles in cellular processes, owing to their essential requirement for chromatin homeostasis. By establishing permissive or repressive chromatin states, histone chaperones control gene expression in a broad sense but also guide context-specific processes such as cell-fate decisions or cellular adaptations ( Cheloufi et al, 2015 ; Chen et al, 2020 ; Hammond et al, 2017 ; Li and Jiao, 2017 ). Here, we show that Hir1 determines chromatin landscapes accessible for transcription of genes that fine-tune responses to nitrogen sources.…”

Section: Discussionmentioning

confidence: 99%

“…The function of HIR orthologs in transcription control is well established in higher eukaryotes ( Hammond et al, 2017 ). Consequently, loss of Hira alters transcriptional dynamics and chromatin accessibility in different cellular contexts ( Chen et al, 2020 ; Nashun et al, 2015 ). Of note, the C. albicans HIR complex exploits related mechanisms during fungal transitions from the unicellular yeast state to hyphal growth, whereby HIR1 deficiency alters the amplitudes of hyphal-specific gene expression ( Jenull et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

The histone chaperone HIR maintains chromatin states to control nitrogen assimilation and fungal virulence

et al. 2021

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The histone chaperone HIR maintains chromatin states to control nitrogen assimilation and fungal virulence Graphical abstract Highlights d The HIR histone chaperone controls nutritional adaptation and fungal virulence d HIR1 modulates chromatin accessibility and transcription of metabolic genes d Innate immune cells show impaired recognition of fungal pathogens lacking HIR1 d Genetic ablation of HIR drives hypervirulence in systemic fungal infections

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“…Recently, the histone chaperone HIRA, responsible for depositing H3.3 onto chromatin, was shown to be pivotal for nucleosome remodeling in HSCs. Its depletion results in an overall decrease in chromatin accessibility and impaired HSC differentiation by hindrance of the transcription of genes coding for critical hematopoietic TFs [53].…”

Section: Histone Variants Modulate Chromatin Accessibility During Hematopoiesismentioning

confidence: 99%

Epigenetic Regulators as the Gatekeepers of Hematopoiesis

2021

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HIRA, a DiGeorge Syndrome Candidate Gene, Confers Proper Chromatin Accessibility on HSCs and Supports All Stages of Hematopoiesis

Cited by 18 publications

References 69 publications

The histone H3.3 chaperone HIRA restrains erythroid-biased differentiation of adult hematopoietic stem cells

The histone H3.3 chaperone HIRA restrains erythroid-biased differentiation of adult hematopoietic stem cells

The histone chaperone HIR maintains chromatin states to control nitrogen assimilation and fungal virulence

Epigenetic Regulators as the Gatekeepers of Hematopoiesis

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