ArticleProceedings of the National Academy of Sciences of the United States of America2021
DOT1L complex regulates transcriptional initiation in human erythroleukemic cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
- Review
- The MLLT3 YEATS domain binds histone marks (H3K9/18/27ac/cr) and ncRNA (7SK), linking transcription and RNA signaling to regulate hematopoiesis.Cell reports · 2026Article
- Histone methyltransferase DOT1L differentially affects the development of dendritic cell subsets.Life science alliance · 2026Article
- Coming to light: the transcriptional regulatory roles of histone lysine crotonylation in health and disease.Cellular & molecular biology letters · 2026Review
- Dual function of DOT1L suppresses tumor cell-intrinsic immunogenicity in hepatocellular carcinoma.Oncogene · 2026Article
- PAF1C restores transcription after DNA damage independently of promoting histone mark deposition.EMBO reports · 2026Article
- PICALM::MLLT10 translocated leukemia.FEBS letters · 2026Review
- TRMT6 mitigates susceptibility and progression of DSS-induced colitis multifacetedly via translational regulation.Scientific reports · 2026Article
- DOT1L activity limits transcription elongation velocity and favors RNAPII pausing to facilitate mutagenesis by AID.Nature communications · 2026Article
- Loss of DOT1L disrupts neuronal transcription and leads to a neurodevelopmental disorder.Brain : a journal of neurology · 2026Article
- Histone methyltransferase DOT1L maintains cell state and restricts cytotoxic potential of CD8 T cells.Science advances · 2025Article
- DOT1L as a Therapeutic Target: Insights into Epigenetic Regulation and Cancer Treatment.Biomolecules & therapeutics · 2025Review
- The MLLT3 YEATS domain is a dual reader of histone marks (H3K9/18/27ac/cr) and ncRNA (7SK), linking epigenetic and RNA signaling to regulate hematopoiesis.bioRxiv : the preprint server for biology · 2025Article
- Discovery of the first-in-class DOT1L PROTAC degrader.European journal of medicinal chemistry · 2025Article
- Loss of DOT1L disrupts neuronal transcription, behavior, and leads to a neurodevelopmental disorder.medRxiv : the preprint server for health sciences · 2025Article
- Transcription-replication conflicts drive R-loop-dependent nucleosome eviction and require DOT1L activity for transcription recovery.Nucleic acids research · 2025Article
- Chromatin environment-dependent effects of DOT1L on gene expression in male germ cells.Communications biology · 2025Article
- DOT1L-mediated RAP80 methylation promotes BRCA1 recruitment to elicit DNA repair.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The emerging role of DOT1L in cell proliferation and differentiation: Friend or foe.Histology and histopathology · 2024Review
- The disruptor of telomeric silencing 1-like (DOT1L) promotes peritoneal fibrosis through the upregulation and activation of protein tyrosine kinases.Molecular biomedicine · 2024Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
DOT1L, the only H3K79 methyltransferase in human cells and a homolog of the yeast Dot1, normally forms a complex with AF10, AF17, and ENL or AF9, is dysregulated in most cases of mixed-lineage leukemia (MLLr), and has been believed to regulate transcriptional elongation on the basis of its colocalization with RNA polymerase II (Pol II), the sharing of subunits (AF9 and ENL) between the DOT1L and super elongation complexes, and the distribution of H3K79 methylation on both promoters and transcribed regions of active genes. Here we show that DOT1L depletion in erythroleukemic cells reduces its global occupancy without affecting the traveling ratio or the elongation rate (assessed by 4sUDRB-seq) of Pol II, suggesting that DOT1L does not play a major role in elongation in these cells. In contrast, analyses of transcription initiation factor binding reveal that DOT1L and ENL depletions each result in reduced TATA binding protein (TBP) occupancies on thousands of genes. More importantly, DOT1L and ENL depletions concomitantly reduce TBP and Pol II occupancies on a significant fraction of direct (DOT1L-bound) target genes, indicating a role for the DOT1L complex in transcription initiation. Mechanistically, proteomic and biochemical studies suggest that the DOT1L complex may regulate transcriptional initiation by facilitating the recruitment or stabilization of transcription factor IID, likely in a monoubiquitinated H2B (H2Bub1)-enhanced manner. Additional studies show that DOT1L enhances H2Bub1 levels by limiting recruitment of the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex. These results advance our understanding of roles of the DOT1L complex in transcriptional regulation and have important implications for MLLr leukemias.
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