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Dynamic changes in histone-methylation 'marks' across the locus encoding interferon-γ during the differentiation of T helper type 2 cells
Abstract
The 'histone-code' hypothesis proposes that cell fate 'decisions' are achieved through the creation of stable epigenetic histone 'marks' at gene loci. Here we explored the formation of marks of repressive methylation of histone 3 at lysine 9 (H3-K9) and of H3-K27 at the locus encoding interferon-gamma (Ifng locus) during the commitment of naive T cells to the T helper type 1 (TH1) and TH2 lineages. Methylation of H3-K9 across the Ifng locus was rapidly induced in differentiating TH1 and TH2 cells and was sustained in TH1 cells. In contrast, TH2 differentiation caused loss of methylation of H3-K9 and gain of methylation of H3-K27 by mechanisms dependent on the transcription factors GATA-3 and STAT6. Thus, histone-methylation marks at the Ifng locus are highly dynamic, which may ensure higher-order transcriptional regulation during early lineage commitment.
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“Two independent studies of patients undergoing allogeneic HSC transplant for haematological malignancies reported that the presence of DNMT3A mutant CH in the donor cell product was associated with reduced risk of disease relapse and increased risk of chronic graft-versus-host disease (GVHD) 152,155 .”
From Clonal haematopoiesis and dysregulation of the immune system (2023) · cites this paper as [155]
In the citing paper
“Recent observations indicate that CH can affect outcomes in patients receiving cellular therapies for haematological malignancies.”
From Clonal haematopoiesis and dysregulation of the immune system (2023) · cites this paper as [155]
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Metadata
- Authors
- Chang, S., & Aune, T. M.
- Venue
- Nature Immunology
- Published
- 2007-06-03
- Volume
- 8
- Issue
- 7
- Pages
- 723-731
- ISSN
- 1529-2908
- 1529-2916
- Cited by
- 149
- References
- 53
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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