| First Author | Guo P | Year | 2022 |
| Journal | Nat Cell Biol | Volume | 24 |
| Issue | 1 | Pages | 99-111 |
| PubMed ID | 34961794 | Mgi Jnum | J:318597 |
| Mgi Id | MGI:6860495 | Doi | 10.1038/s41556-021-00795-7 |
| Citation | Guo P, et al. (2022) Histone variant H3.3 maintains adult haematopoietic stem cell homeostasis by enforcing chromatin adaptability. Nat Cell Biol 24(1):99-111 |
| abstractText | Histone variants and the associated post-translational modifications that govern the stemness of haematopoietic stem cells (HSCs) and differentiation thereof into progenitors (HSPCs) have not been well defined. H3.3 is a replication-independent H3 histone variant in mammalian systems that is enriched at both H3K4me3- and H3K27me3-marked bivalent genes as well as H3K9me3-marked endogenous retroviral repeats. Here we show that H3.3, but not its chaperone Hira, prevents premature HSC exhaustion and differentiation into granulocyte-macrophage progenitors. H3.3-null HSPCs display reduced expression of stemness and lineage-specific genes with a predominant gain of H3K27me3 marks at their promoter regions. Concomitantly, loss of H3.3 leads to a reduction of H3K9me3 marks at endogenous retroviral repeats, opening up binding sites for the interferon regulatory factor family of transcription factors, allowing the survival of rare, persisting H3.3-null HSCs. We propose a model whereby H3.3 maintains adult HSC stemness by safeguarding the delicate interplay between H3K27me3 and H3K9me3 marks, enforcing chromatin adaptability. |
