ArticleScientific reports2017
KDM4B-mediated reduction of H3K9me3 and H3K36me3 levels improves somatic cell reprogramming into pluripotency.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- The Multifaceted Roles of Zinc Finger Proteins in Pluripotency and Reprogramming.International journal of molecular sciences · 2025Review
- Epigenetic regulation of reprogramming and pluripotency: insights from histone modifications and their implications for cancer stem cell therapies.Frontiers in cell and developmental biology · 2025Review
- Dissecting gene activation and chromatin remodeling dynamics in single human cells undergoing reprogramming.Cell reports · 2024Article
- KDM4B down-regulation facilitated breast cancer cell stemness via PHGDH upregulation in H3K36me3-dependent manner.Molecular and cellular biochemistry · 2024Article
- Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming.Nature aging · 2024Review
- Unreprogrammed H3K9me3 prevents minor zygotic genome activation and lineage commitment in SCNT embryos.Nature communications · 2023Article
- Diverse heterochromatin states restricting cell identity and reprogramming.Trends in biochemical sciences · 2023Review
- Methylation of the JMJD2B epigenetic regulator differentially affects its ability to coactivate the ETV1 and JUN transcription factors.International journal of biochemistry and molecular biology · 2023Article
- The dynamics of chromatin states mediated by epigenetic modifications during somatic cell reprogramming.Frontiers in cell and developmental biology · 2023Review
- KDM4 Demethylases: Structure, Function, and Inhibitors.Advances in experimental medicine and biology · 2023Article
- OCT4 activates a Suv39h1-repressive antisense lncRNA to couple histone H3 Lysine 9 methylation to pluripotency.Nucleic acids research · 2022Article
- Chromatin accessibility dynamics during cell fate reprogramming.EMBO reports · 2021Review
- Context-Dependent Requirement of Euchromatic Histone Methyltransferase Activity during Reprogramming to Pluripotency.Stem cell reports · 2020Article
- Heterochromatin establishment during early mammalian development is regulated by pericentromeric RNA and characterized by non-repressive H3K9me3.Nature cell biology · 2020Article
- Listening to mother: Long-term maternal effects in mammalian development.Molecular reproduction and development · 2020Review
- Cloning and Expression Analysis of Two Kdm Lysine Demethylases in the Testes of Mature Yaks and Their Sterile Hybrids.Animals : an open access journal from MDPI · 2020Article
- Reprogramming: identifying the mechanisms that safeguard cell identity.Development (Cambridge, England) · 2019Review
- Characterization and comparative analyses of transcriptomes of cloned andBiology open · 2019Article
- The role of α-ketoglutarate-dependent proteins in pluripotency acquisition and maintenance.The Journal of biological chemistry · 2019Review
- Transcriptional defects and reprogramming barriers in somatic cell nuclear reprogramming as revealed by single-embryo RNA sequencing.BMC genomics · 2018Article
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Authors and funding
7 authors.
Funding
Abstract
Correct reprogramming of epigenetic marks is essential for somatic cells to regain pluripotency. Repressive histone (H) lysine (K) methylation marks are known to be stable and difficult to reprogram. In this study, we generated transgenic mice and mouse embryonic fibroblasts (MEFs) for the inducible expression of KDM4B, a demethylase that removes H3 K9 and H3K36 trimethylation (me3) marks (H3K9/36me3). Upon inducing Kdm4b, H3K9/36me3 levels significantly decreased compared to non-induced controls. Concurrently, H3K9me1 levels significantly increased, while H3K9me2 and H3K27me3 remained unchanged. The global transcriptional impact of Kdm4b-mediated reduction in H3K9/36me3 levels was examined by comparative microarray analysis and mRNA-sequencing of three independent transgenic MEF lines. We identified several commonly up-regulated targets, including the heterochromatin-associated zinc finger protein 37 and full-length endogenous retrovirus repeat elements. Following optimized zona-free somatic nuclear transfer, reduced H3K9/36me3 levels were restored within hours. Nevertheless, hypo-methylated Kdm4b MEF donors reprogrammed six-fold better into cloned blastocysts than non-induced donors. They also reprogrammed nine-fold better into induced pluripotent stem cells that gave rise to teratomas and chimeras. In summary, we firmly established H3K9/36me3 as a major roadblock to somatic cell reprogramming and identified transcriptional targets of derestricted chromatin that could contribute towards improving this process in mouse.
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