HELLS is required for DNA methylation at human satellite repeats [RNA-seq]
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ABSTRACT:
PROVIDER: PRJNA1259059 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:HELLS is required for DNA methylation at human satellite repeats
| PRJNA1055544 | ENA
Project description:HELLS is a known chromatin remodeler, but its specific genomic targets have not been sufficiently described. Here, we report the generation of HELLS knockout human pluripotent cells and through telomere-to-telomere mapping of whole genome bisulfite sequencing data combined with ATAC-sequencing, we discovered a striking loss of DNA methylation over inaccessible, satellite repeats. Our study further clarifies the role of HELLS and provides insights into functional consequences through its deregulation in diseases.
2025-06-23 | GSE296398 | GEO
Project description:DNA methylation is essential for genome integrity and involves multi-layered chromatin interac-tions that require remodeling proteins like the Helicase, Lymphoid-specific (HELLS). Here, we generate HELLS and de novo DNA methyltransferase 3 A and B (DNMT3A/B) knockout human pluripotent stem cells and assemble telomere-to-telomere maps of whole genome bisulfite se-quencing data combined with ATAC-sequencing. Disrupting HELLS induces a global loss of DNA methylation that is distinct from the de novo DNMTs, in particular over peri/centromeric satellite repeats as defined in the telomere-to-telomere genome assembly. However, HELLS is dispen-sable for local enhancer remodeling and the potential to differentiate into the three germ layers. Taken together, these findings further clarify the genomic targets and role of HELLS in human cells.
2025-06-23 | GSE241688 | GEO
Project description:interactions that require remodeling proteins like the Helicase, Lymphoid-specific (HELLS). Here, we generate HELLS and de novo DNA methyltransferase 3 A and B (DNMT3A/B) knockout hu-man pluripotent stem cells and assemble telomere-to-telomere maps of whole genome bisulfite sequencing data combined with ATAC-sequencing. Disrupting HELLS induces a global loss of DNA methylation that is distinct from the de novo DNMTs, in particular over peri/centromeric satellite repeats as defined in the telomere-to-telomere genome assembly. However, HELLS is dispensable for local enhancer remodeling and the potential to differentiate into the three germ layers. Taken together, these findings further clarify the genomic targets and role of HELLS in human cells.
2025-06-23 | GSE250465 | GEO
Project description:Inheritance and reprogramming of non-CG methylation at satellite DNA repeats
| PRJNA628650 | ENA
Project description:In vertebrates, DNA methylation predominantly occurs at CG dinucleotides however, widespread non-CG methylation (mCH) has been reported in mammalian embryonic stem cells and in the brain. In mammals, mCH is found at CAC trinucleotides in the nervous system, where it is associated with transcriptional repression, and at CAG trinucleotides in embryonic stem cells, where it positively correlates with transcription. Moreover, CAC methylation appears to be a conserved feature of adult vertebrate brains. Unlike any of those methylation signatures, here we describe a novel form of mCH that occurs in the TGCT context within zebrafish mosaic satellite repeats. TGCT methylation is inherited from both male and female gametes, remodelled during mid-blastula transition, and re-established during gastrulation in all embryonic layers. Moreover, we identify DNA methyltransferase 3ba (Dnmt3ba) as the primary enzyme responsible for the deposition of this mCH mark. Finally, we observe that TGCT-methylated repeats are specifically associated with H3K9me3-marked heterochromatin suggestive of a functional interplay between these two gene-regulatory marks. Altogether, this work provides insight into a novel form of vertebrate mCH and highlights the substrate diversity of vertebrate DNA methyltransferases.
2020-05-26 | GSE149416 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-06-23 | GSE251848 | GEO
Project description: Not available
| S-EPMC12273238 | biostudies-literature
Project description:During meiosis, chromosomes must find, pair and synapse with their homologous partner in the crowded milieu of the nucleus, without being entangled by non-homologous chromosomes1. Generally, homology detection is thought to rely on recombination between the homologous chromosomes. However, pairing and synapsis can occur in the absence of recombination2–10, suggesting alternate mechanisms which discriminate between homologous and non-homologous associations. In many eukaryotes, tandem repeats known as satellite DNA are known to facilitate inter-chromosomal associations11. Notably, their non-uniform distribution across chromosomes gives rise to homologue-specific satellite DNA ‘barcodes’12–14, which have been speculated to enable meiotic pairing15–18. However, the inability to manipulate these repeats in most model organisms means that satellite DNA function in meiotic pairing remains actively debated. Here, we use satellite DNA deletion, duplication, and translocation strains that are unique to Drosophila to demonstrate that repeat mismatches perturb meiotic pairing, particularly at centromeres and pericentromeres. Strains containing satellite DNA mismatches exhibit pairing defects that are likely driven by the incorrect association of similar repeats on non-homologous chromosomes. Notably, defective pairing also occurs in the progeny of D. melanogaster natural populations that have diverged in their satellite DNA content. In the absence of homozygous satellite DNA arrays, we further show that pairing is antagonized by the HORMAD protein, Mad2, while a Pachytene checkpoint 2 (Pch2)-dependent meiotic delay can restore pairing. Finally, compromised meiotic pairing is strongly correlated with mid-oogenesis cell death, a quality control mechanism that likely culls defective oocytes to prevent chromosome mis-segregation and aneuploidy. Therefore, our findings resolve the debate on satellite DNA functionality by providing evidence for a role in meiotic pairing. We propose that this repeat-based pairing mechanism exerts an underappreciated selective pressure, constraining the divergence of these rapidly evolving tandem repeats within interbreeding natural populations.
2026-05-21 | GSE332787 | GEO
Project description:Meiotic pairing through barcode-like satellite DNA repeats
| PRJNA1469082 | ENA