ArticleEpigenetics & chromatin2018
Individual retrotransposon integrants are differentially controlled by KZFP/KAP1-dependent histone methylation, DNA methylation and TET-mediated hydroxymethylation in naïve embryonic stem cells.
Article in Epigenetics & chromatin, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Pooled it
- The Multifaceted Roles of Zinc Finger Proteins in Pluripotency and Reprogramming.International journal of molecular sciences · 2025Review
- Decoding Aging through iPSC Reprogramming: Advances and Challenges.Aging and disease · 2025Review
- Transposable elements may enhance antiviral resistance in HIV-1 elite controllers.Genome biology · 2025Article
- TDP-43 chronic deficiency leads to dysregulation of transposable elements and gene expression by affecting R-loop and 5hmC crosstalk.Cell reports · 2024Article
- Transposable elements may enhance antiviral resistance in HIV-1 elite controllers.bioRxiv : the preprint server for biology · 2023Article
- Characterization of H3K9me3 and DNA methylation co-marked CpG-rich regions during mouse development.BMC genomics · 2023Article
- Review
- Dynamic DNA 5-hydroxylmethylcytosine and RNA 5-methycytosine Reprogramming During Early Human Development.Genomics, proteomics & bioinformatics · 2023Article
- Transposable elements in early human embryo development and embryo models.Current opinion in genetics & development · 2023Review
- Structure and functional mapping of the KRAB-KAP1 repressor complex.The EMBO journal · 2022Article
- Transposon control as a checkpoint for tissue regeneration.Development (Cambridge, England) · 2022Article
- Acute deletion of TET enzymes results in aneuploidy in mouse embryonic stem cells through decreased expression of Khdc3.Nature communications · 2022Article
- Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors.Development (Cambridge, England) · 2022Article
- DNA methyltransferases are complementary in maintaining DNA methylation in embryonic stem cells.iScience · 2022Article
- RIF1 and KAP1 differentially regulate the choice of inactive versus active X chromosomes.The EMBO journal · 2021Article
- A bipartite element with allele-specific functions safeguards DNA methylation imprints at the Dlk1-Dio3 locus.Developmental cell · 2021Article
- Article
- Early-life social experience affects offspring DNA methylation and later life stress phenotype.Nature communications · 2021Article
- Elevated retrotransposon activity and genomic instability in primed pluripotent stem cells.Genome biology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe KZFP/KAP1 (KRAB zinc finger proteins/KRAB-associated protein 1) system plays a central role in repressing transposable elements (TEs) and maintaining parent-of-origin DNA methylation at imprinting control regions (ICRs) during the wave of genome-wide reprogramming that precedes implantation. In naïve murine embryonic stem cells (mESCs), the genome is maintained highly hypomethylated by a combination of TET-mediated active demethylation and lack of de novo methylation, yet KAP1 is tethered by sequence-specific KZFPs to ICRs and TEs where it recruits histone and DNA methyltransferases to impose heterochromatin formation and DNA methylation.
resultsHere, upon removing either KAP1 or the cognate KZFP, we observed rapid TET2-dependent accumulation of 5hmC at both ICRs and TEs. In the absence of the KZFP/KAP1 complex, ICRs lost heterochromatic histone marks and underwent both active and passive DNA demethylation. For KAP1-bound TEs, 5mC hydroxylation correlated with transcriptional reactivation. Using RNA-seq, we further compared the expression profiles of TEs upon Kap1 removal in wild-type, Dnmt and Tet triple knockout mESCs. While we found that KAP1 represents the main effector of TEs repression in all three settings, we could additionally identify specific groups of TEs further controlled by DNA methylation. Furthermore, we observed that in the absence of TET proteins, activation upon Kap1 depletion was blunted for some TE integrants and increased for others.
conclusionsOur results indicate that the KZFP/KAP1 complex maintains heterochromatin and DNA methylation at ICRs and TEs in naïve embryonic stem cells partly by protecting these loci from TET-mediated demethylation. Our study further unveils an unsuspected level of complexity in the transcriptional control of the endovirome by demonstrating often integrant-specific differential influences of histone-based heterochromatin modifications, DNA methylation and 5mC oxidation in regulating TEs expression.
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