ArticleNature communications2020
LSH mediates gene repression through macroH2A deposition.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- Dysregulated HELLS expression alters cellular processes and serves as a potential prognostic marker in acute myeloid leukemia.The Journal of biological chemistry · 2026Article
- Major alleles of CDCA7 shape CG methylation in Arabidopsis thaliana.Nature plants · 2025Article
- Ubiquitination of the histone variant mH2A1.2 prevents toxic RAD18 accumulation at a subset of genomic loci upon replication stress.Molecular cell · 2025Article
- Review
- Multifunctional histone variants in genome function.Nature reviews. Genetics · 2025Review
- Molecular and structural basis of the chromatin remodeling activity by Arabidopsis DDM1.Nature communications · 2024Article
- HELLS regulates transcription in T-cell lymphomas by reducing unscheduled R-loops and by facilitating RNAPII progression.Nucleic acids research · 2024Article
- Induced proximity labeling and editing for epigenetic research.Cell chemical biology · 2024Review
- Context-specific functions of chromatin remodellers in development and disease.Nature reviews. Genetics · 2024Review
- Histone H2A variants play a key role at DNA double-strand breaks during repair pathway choice.Frontiers in epigenetics and epigenomics · 2024Review
- Coevolution of the CDCA7-HELLS ICF-related nucleosome remodeling complex and DNA methyltransferases.eLife · 2023Article
- Germinal center output is sustained by HELLS-dependent DNA-methylation-maintenance in B cells.Nature communications · 2023Article
- Article
- Coevolution of the CDCA7-HELLS ICF-related nucleosome remodeling complex and DNA methyltransferases.bioRxiv : the preprint server for biology · 2023Article
- Chromatin remodeling of histone H3 variants underlies epigenetic inheritance of DNA methylation.bioRxiv : the preprint server for biology · 2023Article
- Article
- New genetic and epigenetic insights into the chemokine system: the latest discoveries aiding progression toward precision medicine.Cellular & molecular immunology · 2023Review
- Seminars in cell and development biology on histone variants remodelers of H2A variants associated with heterochromatin.Seminars in cell & developmental biology · 2023Review
- Histone H2A variants: Diversifying chromatin to ensure genome integrity.Seminars in cell & developmental biology · 2023Review
- Histone Variants in the Specialization of Plant Chromatin.Annual review of plant biology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
The human Immunodeficiency Centromeric Instability Facial Anomalies (ICF) 4 syndrome is a severe disease with increased mortality caused by mutation in the LSH gene. Although LSH belongs to a family of chromatin remodeling proteins, it remains unknown how LSH mediates its function on chromatin in vivo. Here, we use chemical-induced proximity to rapidly recruit LSH to an engineered locus and find that LSH specifically induces macroH2A1.2 and macroH2A2 deposition in an ATP-dependent manner. Tethering of LSH induces transcriptional repression and silencing is dependent on macroH2A deposition. Loss of LSH decreases macroH2A enrichment at repeat sequences and results in transcriptional reactivation. Likewise, reduction of macroH2A by siRNA interference mimicks transcriptional reactivation. ChIP-seq analysis confirmed that LSH is a major regulator of genome-wide macroH2A distribution. Tethering of ICF4 mutations fails to induce macroH2A deposition and ICF4 patient cells display reduced macroH2A deposition and transcriptional reactivation supporting a pathogenic role for altered marcoH2A deposition. We propose that LSH is a major chromatin modulator of the histone variant macroH2A and that its ability to insert marcoH2A into chromatin and transcriptionally silence is disturbed in the ICF4 syndrome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.