MLL-AF4 Spreading Identifies Binding Sites that Are Distinct from Super-Enhancers and that Govern Sensitivity to DOT1L Inhibition in Leukemia
Sign Up to like & getrecommendations! Published in 2017 at "Cell Reports"
DOI: 10.1016/j.celrep.2016.12.054
Abstract: Summary Understanding the underlying molecular mechanisms of defined cancers is crucial for effective personalized therapies. Translocations of the mixed-lineage leukemia (MLL) gene produce fusion proteins such as MLL-AF4 that disrupt epigenetic pathways and cause poor-prognosis… read more here.
Keywords: mll af4; af4 spreading; sensitivity; gene ... See more keywords
DOT1L O-GlcNAcylation promotes its protein stability and MLL-fusion leukemia cell proliferation.
Sign Up to like & getrecommendations! Published in 2021 at "Cell reports"
DOI: 10.1016/j.celrep.2021.109739
Abstract: Histone lysine methylation functions at the interface of the extracellular environment and intracellular gene expression. DOT1L is a versatile histone H3K79 methyltransferase with a prominent role in MLL-fusion leukemia, yet little is known about how… read more here.
Keywords: mll fusion; fusion leukemia; dot1l;
Structural Basis of Dot1L Stimulation by Histone H2B Lysine 120 Ubiquitination.
Sign Up to like & getrecommendations! Published in 2019 at "Molecular cell"
DOI: 10.1016/j.molcel.2019.03.029
Abstract: The essential histone H3 lysine 79 methyltransferase Dot1L regulates transcription and genomic stability and is deregulated in leukemia. The activity of Dot1L is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120Ub); however, the… read more here.
Keywords: lysine 120; histone h2b; h2b lysine; histone ... See more keywords
Methylation of Histone H3K79 by Dot1L Requires Multiple Contacts with the Ubiquitinated Nucleosome.
Sign Up to like & getrecommendations! Published in 2019 at "Molecular cell"
DOI: 10.1016/j.molcel.2019.05.013
Abstract: Cryo-EM structures of Dot1L in complex with a ubiquitinated nucleosome provide the long-sought-after molecular mechanism of Dot1L-mediated methylation of lysine 79 in histone H3 and explain crosstalk with histone H2B ubiquitination. read more here.
Keywords: histone h3k79; ubiquitinated nucleosome; methylation histone; histone ... See more keywords
Computer-Aided Discovery of Massonianoside B as a Novel Selective DOT1L Inhibitor.
Sign Up to like & getrecommendations! Published in 2019 at "ACS chemical biology"
DOI: 10.1021/acschembio.8b00933
Abstract: Protein methyltransferases (PMTs) are involved in numerous biological processes and have been studied as a promising target class in the field of oncology and other diseases. Disruptor of telomeric silencing 1-like (DOT1L), a histone H3… read more here.
Keywords: massonianoside; dot1l inhibitor; discovery; mll ... See more keywords
Structural basis of the crosstalk between histone H2B monoubiquitination and H3 lysine 79 methylation on nucleosome
Sign Up to like & getrecommendations! Published in 2019 at "Cell Research"
DOI: 10.1038/s41422-019-0146-7
Abstract: Dear Editor, Histone marks deposited by post-translational modifications (PTMs) frequently occur in interrelated combinational patterns to create a complex and precise control on the chromatin structure and function. One of the landmark findings of histone… read more here.
Keywords: surface; supplementary information; h2b; fig ... See more keywords
Analysis of Polymorphisms in the MATN3 and DOT1L Genes and CTX-II Urinary Levels in Patients with Knee Osteoarthritis in a Northeast Mexican-Mestizo Population.
Sign Up to like & getrecommendations! Published in 2020 at "Genetic testing and molecular biomarkers"
DOI: 10.1089/gtmb.2019.0179
Abstract: Aims: To investigate the possible roles of the single nucleotide polymorphisms (SNPs) MATN3 (rs77245812) and DOT1L (rs12982744) with susceptibility to knee osteoarthritis (KOA) among mestizos from the northeast region of Mexico. In addition, we analyzed… read more here.
Keywords: urinary levels; mestizo population; knee osteoarthritis; matn3 ... See more keywords
DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex
Sign Up to like & getrecommendations! Published in 2019 at "Nucleic Acids Research"
DOI: 10.1093/nar/gky953
Abstract: Abstract Cortical development is controlled by transcriptional programs, which are orchestrated by transcription factors. Yet, stable inheritance of spatio-temporal activity of factors influencing cell fate and localization in different layers is only partly understood. Here… read more here.
Keywords: transcriptional programs; layer; layer identity; upper layer ... See more keywords
Inhibition of histone methyltransferase DOT1L silences ERα gene and blocks proliferation of antiestrogen-resistant breast cancer cells
Sign Up to like & getrecommendations! Published in 2019 at "Science Advances"
DOI: 10.1126/sciadv.aav5590
Abstract: Pharmacological inhibition of DOT1L blocks estrogen receptor signaling in breast cancer. Breast cancer (BC) resistance to endocrine therapy results from constitutively active or aberrant estrogen receptor α (ERα) signaling, and ways to block ERα pathway… read more here.
Keywords: methyltransferase dot1l; gene; dot1l; breast cancer ... See more keywords
P101 DOT1L inhibition increases dermal fibroblast proliferation but has no effects on in vitro or in vivo collagen deposition in models of fibrosis
Sign Up to like & getrecommendations! Published in 2018 at "Annals of the Rheumatic Diseases"
DOI: 10.1136/annrheumdis-2018-ewrr2018.117
Abstract: Introduction Fibrosis is a key process in Systemic Sclerosis, a devastating disease that is not well understood. The role of epigenetic disease mechanisms is increasingly explored. DOT1L, the unique H3K79-methyltransferase, methylates histone 3 at the… read more here.
Keywords: collagen; fibrosis; dot1l inhibition; proliferation ... See more keywords
DOT1L Is a Novel Cancer Stem Cell Target for Triple-Negative Breast Cancer
Sign Up to like & getrecommendations! Published in 2022 at "Clinical Cancer Research"
DOI: 10.1158/1078-0432.ccr-21-1299
Abstract: Abstract Purpose: Although chemotherapies kill most cancer cells, stem cell–enriched survivors seed metastasis, particularly in triple-negative breast cancers (TNBC). TNBCs arise from and are enriched for tumor stem cells. Here, we tested if inhibition of… read more here.
Keywords: stem cell; dot1l; aldh1 aldh1; stem ... See more keywords