ArticleEpigenetics & chromatin2020
The histone methyltransferase Setd8 alters the chromatin landscape and regulates the expression of key transcription factors during erythroid differentiation.
Article in Epigenetics & chromatin, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- KMT5A maintains muscle stem cell quiescence through epigenetic regulation of Notch signaling.iScience · 2026Article
- The H3K4 methyltransferase KMT2D is an essential cofactor for GATA1 at erythroid gene enhancers.Nature communications · 2026Article
- NFYB-lncRNA axis resets the tumor microenvironment to promote HCC aggressive progression by a positive feedback loop.Acta pharmaceutica Sinica. B · 2026Article
- Post-translational Modifications in Proteins: Prediction Methods, Biological Functions, and Diseases.MedComm · 2026Review
- Dynamic changes in Lamin B1 and heterochromatin coincide with chromatin condensation during human erythropoiesis.Genome biology · 2026Article
- Histone modifications in the regulation of erythropoiesis.Annals of medicine · 2025Review
- Histone H4 lysine 20 methylation marks genes dynamically regulated during erythroid maturation.Epigenetics & chromatin · 2025Article
- Lactate regulates cell differentiation of erythroid progenitor cells via histone lactylation modification.iScience · 2025Article
- The Condensin II complex regulates essential gene expression programs during erythropoiesis.Development (Cambridge, England) · 2025Article
- The role(s) of NF-Y in development and differentiation.Cell death and differentiation · 2025Review
- Targeting the epigenome to reinvigorate T cells for cancer immunotherapy.Military Medical Research · 2023Review
- H4K20me1 plays a dual role in transcriptional regulation of regeneration and axis patterning inLife science alliance · 2023Article
- The Haematopoietically-expressed homeobox transcription factor: roles in development, physiology and disease.Frontiers in immunology · 2023Review
- Arid1a mutation suppresses TGF-β signaling and induces cholangiocarcinoma.Cell reports · 2022Article
- Epigenetic and Transcriptional Control of Erythropoiesis.Frontiers in genetics · 2022Review
- Regulation of RNA polymerase II activity is essential for terminal erythroid maturation.Blood · 2021Article
- Impairment of human terminal erythroid differentiation by histone deacetylase 5 deficiency.Blood · 2021Article
- Epigenetic modifiers in normal and aberrent erythropoeisis.Seminars in hematology · 2021Review
- Codanin-1 mutations engineered in human erythroid cells demonstrate role of CDAN1 in terminal erythroid maturation.Experimental hematology · 2020Article
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6 authors at 2 institutions in 1 country.
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Abstract
backgroundSETD8 is the sole methyltransferase capable of mono-methylating histone H4, lysine 20. SETD8 and H4K20me1 play a role in a number of essential biologic processes, including cell cycle progression, establishment of higher order chromatin structure, and transcriptional regulation. SETD8 is highly expressed in erythroid cells and erythroid deletion of Setd8 is embryonic lethal by embryonic day 11.5 (E11.5) due to profound anemia, suggesting that it has an erythroid-specific function. The function of SETD8 in the hemopoietic system is poorly understood. The goal of our study was to gain insights into the function of SETD8 during erythroid differentiation.
resultsWe performed ATAC-seq (assay for transposase-accessible chromatin) on sorted populations of E10.5 Setd8 mutant and control erythroblasts. Accessibility profiles were integrated with expression changes and a mark of heterochromatin (H3K27me3) performed in wild-type E10.5 erythroblasts to further understand the role of SETD8 in erythropoiesis. Data integration identified regions of greater chromatin accessibility in Setd8 mutant cells that co-located with H3K27me3 in wild-type E10.5 erythroblasts suggesting that these regions, and their associated genes, are repressed during normal erythropoiesis. The majority of these more accessible regions were located in promoters and they frequently co-located with the NFY complex. Pathway analysis of genes identified through data integration revealed stemness-related pathways. Among those genes were multiple transcriptional regulators active in multipotent progenitors, but repressed during erythroid differentiation including Hhex, Hlx, and Gata2. Consistent with a role for SETD8 in erythroid specification, SETD8 expression is up-regulated upon erythroid commitment, and Setd8 disruption impairs erythroid colony forming ability.
conclusionTaken together, our results suggest that SETD8 is an important regulator of the chromatin landscape during erythroid differentiation, particularly at promoters. Our results also identify a novel role for Setd8 in the establishment of appropriate patterns of lineage-restricted gene expression during erythroid differentiation.
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