ArticlePLoS genetics2013
Ash1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract polycomb silencing.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Role of Ash1l in Tourette syndrome and other neurodevelopmental disorders.Developmental neurobiology · 2021Pooled it
- A novel de novo missense variant in ASH1L associated with mild autism spectrum disorder and an uneven cognitive profile: a case report.Journal of medical case reports · 2025Article
- Role of Histone H3 Lysine 4 Methylation in Chromatin Biology.Molecules (Basel, Switzerland) · 2025Review
- CircSHOC2 regulates steroid hormone synthesis in ovarian granulosa cells through the mir-130b-5p/ASH1L pathway.Zoological research · 2025Article
- Histone methyltransferase ASH1L primes metastases and metabolic reprogramming of macrophages in the bone niche.Nature communications · 2025Article
- Structure-function relationship of ASH1L and histone H3K36 and H3K4 methylation.Nature communications · 2025Article
- Structure-Based Development of Novel Spiro-Piperidine ASH1L Inhibitors.Journal of medicinal chemistry · 2025Article
- Loss-of-function mutations of microRNA-142-3p promoteWorld journal of gastroenterology · 2025Article
- Thioamides in medicinal chemistry and as small molecule therapeutic agents.European journal of medicinal chemistry · 2024Review
- Systematic perturbations of SETD2, NSD1, NSD2, NSD3, and ASH1L reveal their distinct contributions to H3K36 methylation.Genome biology · 2024Article
- ASH1L guards cis-regulatory elements against cyclobutane pyrimidine dimer induction.Nucleic acids research · 2024Article
- Article
- Expanding the molecular landscape of childhood apraxia of speech: evidence from a single-center experience.Frontiers in neuroscience · 2024Article
- ASH1L-MRG15 methyltransferase deposits H3K4me3 and FACT for damage verification in nucleotide excision repair.Nature communications · 2023Article
- Histone lysine methyltransferase-related neurodevelopmental disorders: current knowledge and saRNA future therapies.Frontiers in cell and developmental biology · 2023Review
- Tumor-intrinsic PRC2 inactivation drives a context-dependent immune-desert microenvironment and is sensitized by immunogenic viruses.The Journal of clinical investigation · 2022Article
- The methyltransferase enzymes KMT2D, SETD1B, and ASH1L are key mediators of both metabolic and epigenetic changes during cellular senescence.Molecular biology of the cell · 2022Article
- Article
- Lysine methyltransferase inhibitors: where we are now.RSC chemical biology · 2022Review
- Counteracting epigenetic mechanisms regulate the structural development of neuronal circuitry in human neurons.Molecular psychiatry · 2022Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molecular mechanisms for the establishment of transcriptional memory are poorly understood. 5,6-dichloro-1-D-ribofuranosyl-benzimidazole (DRB) is a P-TEFb kinase inhibitor that artificially induces the poised RNA polymerase II (RNAPII), thereby manifesting intermediate steps for the establishment of transcriptional activation. Here, using genetics and DRB, we show that mammalian Absent, small, or homeotic discs 1-like (Ash1l), a member of the trithorax group proteins, methylates Lys36 of histone H3 to promote the establishment of Hox gene expression by counteracting Polycomb silencing. Importantly, we found that Ash1l-dependent Lys36 di-, tri-methylation of histone H3 in a coding region and exclusion of Polycomb group proteins occur independently of transcriptional elongation in embryonic stem (ES) cells, although both were previously thought to be consequences of transcription. Genome-wide analyses of histone H3 Lys36 methylation under DRB treatment have suggested that binding of the retinoic acid receptor (RAR) to a certain genomic region promotes trimethylation in the RAR-associated gene independent of its ongoing transcription. Moreover, DRB treatment unveils a parallel response between Lys36 methylation of histone H3 and occupancy of either Tip60 or Mof in a region-dependent manner. We also found that Brg1 is another key player involved in the response. Our results uncover a novel regulatory cascade orchestrated by Ash1l with RAR and provide insights into mechanisms underlying the establishment of the transcriptional activation that counteracts Polycomb silencing.
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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.