• AF10 (MLLT10) prevents somatic cell reprogramming through regulation of DOT1L-mediated H3K79 methylation. (ox.ac.uk)
  • In somatic cells and induced pluripotent stem cells (iPSCs) higher order H3K79 methylation is dependent on AF10 expression. (ox.ac.uk)
  • In AF10 knock-out cells, re-expression wild-type AF10, but not a DOT1L binding-impaired mutant, rescues overall H3K79 methylation and reduces reprogramming efficiency. (ox.ac.uk)
  • CONCLUSIONS: Our findings establish AF10 as a novel barrier to reprogramming by regulating H3K79 methylation and thereby sheds light on the mechanism by which cell identity is maintained in somatic cells. (ox.ac.uk)
  • H3K79 methylation participates in the DNA damage response and has multiple roles in nucleotide excision repair and sister chromatid recombinational repair. (wikipedia.org)
  • In this study, we show that the CALM-AF10 fusion protein can also greatly reduce global H3K79 methylation in both human and murine leukemic cells by disrupting the AF10-mediated association of hDOT1L with chromatin. (utmb.edu)
  • Cells with reduced H3K79 methylation are more sensitive to γ-irradiation and display increased chromosomal instability. (utmb.edu)
  • In addition to its role in H3K36 tri-methylation, SETD2 is required to maintain high H3K79 di-methylation and MLL-AF9-binding to critical target genes, such as Hoxa9 . (nature.com)
  • Although multiple developmental abnormalities in Dot1L-deficient mouse embryos have been studied, the biological function of H3K79 methylation in mammal oocytes remains unclear. (nel.edu)
  • The distribution and level of Dot1L protein and H3K79 methylation were examined using immunofluorescence and western-blot techniques, respectively. (nel.edu)
  • The Dot1l expression and H3K79 methylation level were suppressed effectively with anti-Dot1l siRNA injection. (nel.edu)
  • Dot1L and H3K79 methylation play important roles in meiosis progression and are supposed to be associated with chromosome deacetylation of mouse oocytes. (nel.edu)
  • Here, we report that H3pT11 directly inhibits Dot1-catalyzed H3K79 tri-methylation (H3K79me3) and uncover how this histone crosstalk regulates autophagy and telomere silencing. (nih.gov)
  • Aberrant methylation of H3K79 has been implicated in leukemias. (chinesepeptideco.com)
  • These results demonstrate that H3K79 methylation promotes histone replacement during spermiogenesis . (bvsalud.org)
  • In general methylation of histone H3 lysine 9 (H3K9) H3K27 or H4K20 is definitely linked to formation of tightly packed chromatin and gene silencing whereas methylation on H3K4 H3K36 and H3K79 is definitely associated with actively transcribed areas and gene activation lithospermic acid (9). (sciencepop.org)
  • Specific patterns of H3K79 methylation influence genetic interaction of oncogenes in AML. (thedeshpandelab.com)
  • DOT1L-controlled cell-fate determination and transcription elongation are independent of H3K79 methylation. (alicerutherford.com)
  • Specific mutations functionally compromise DOT1L methyltransferase enzyme activity leading to reduced H3K79 methylation. (ox.ac.uk)
  • Heavy methyl-SILAC (hm-SILAC) was used to further confirm the histone methylation flux (especially for H3K79) during HCMV infection. (princeton.edu)
  • Overall, these results outline a novel interplay between H3K56Ac, H3K79 methylation, and H4K16 acetylation in the cellular response to DNA damage. (johnshopkins.edu)
  • BACKGROUND: The histone H3 lysine 79 (H3K79) methyltransferase DOT1L is a key chromatin-based barrier to somatic cell reprogramming. (ox.ac.uk)
  • The leukemogenic CALM-AF10 fusion protein is capable of interacting with the histone H3 lysine 79 (H3K79)-specific methyltransferase hDOT1L through the fused AF10 moiety. (utmb.edu)
  • Lysine 79 of histone H3 (H3K79) can be methylated specifically by the Dot1 family of histone lysine methyltransferases. (nel.edu)
  • Tumor with mutations in IDH1 or IDH2 had lower 5-hydroxymethylcytosine and higher 5-methylcytosine levels, as well as increased dimethylation of histone H3 lysine 79 (H3K79). (nih.gov)
  • The DOT1L histone H3 lysine 79 (H3K79) methyltransferase plays an oncogenic role in MLL-rearranged leukemogenesis. (ox.ac.uk)
  • DOT1L, the sole histone H3K79 methyltransferase , is essential for embryonic development . (bvsalud.org)
  • Bromo-deaza-SAH is a small molecule inhibitor of the chromatin modifying enzymes DOT1-like histone H3K79 methyltransferase (DOT1L) and DNA (cytosine-5-)-methyltransferase 1 (DNMT1). (guidetopharmacology.org)
  • In contrast to CTCF we found CTCFL highly enriched at 'open' chromatin marked by H3K27 acetylation, H3K4 di- and trimethylation, H3K79 dimethylation and H3K9 acetylation plus the histone variant H2A.Z. CTCFL is enriched at transcriptional start sites and regions bound by transcription factors. (eur.nl)
  • H3K79 dimethylation has been detected in the transcribed regions of active genes. (wikipedia.org)
  • Euchromatin includes less-condensed transcriptional active regions, determined by a depletion of methylated DNA, an enrichment in specifically methylated histones such as H3K4, H3K36, H3K79 and a high level of histone acetylation [ 13 ]. (biomedcentral.com)
  • Here, the distribution of Dot1L, methyltransferase of residue lys79 of histone H3 (H3K79) in mouse, and its effect on mouse oocytes meiosis were investigated to examine whether there are changes in the pattern of distribution and effect of Dot1L on mouse oocytes meiosis. (nel.edu)
  • This interaction leads to local H3K79 hypermethylation on Hoxa5 loci, which up-regulates the expression of Hoxa5 and contributes to leukemogenesis. (utmb.edu)
  • We evaluated DOT1L (the H3K79 methyltransferase) mRNA levels in mock and HCMV-infected cells over a 96 h time course, and observed a significant increase in this methyltransferase as early as 24 hpi showing that viral infection up-regulates DOT1L expression, which drives H3K79me2. (princeton.edu)
  • SETD2 loss synergizes with pharmacologic inhibition of the H3K79 methyltransferase DOT1L to induce DNA damage, growth arrest, differentiation, and apoptosis. (nature.com)
  • Mechanistically, DOT1L facilitates DNA damage repair, with DOT1L-methylated H3K79 involvement in binding and recruiting XPC to the DNA damage site for nucleotide excision repair (NER). (ox.ac.uk)
  • 23. The histone H3K79 methyltransferase Dot1L is essential for mammalian development and heterochromatin structure. (nih.gov)
  • 30. Depletion of H3K79 methyltransferase Dot1L promotes cell invasion and cancer stem-like cell property in ovarian cancer. (nih.gov)
  • 34. Neuronal Dot1l Activity Acts as a Mitochondrial Gene-Repressor Associated with Human Brain Aging via H3K79 Hypermethylation. (nih.gov)
  • As aberrant transcriptional regulators, MLL-fusion proteins alter gene expression in hematopoietic cells through interactions with the histone H3 lysine 79 (H3K79) methyltransferase DOT1L. (nih.gov)
  • Disruptor of telomeric silencing 1-like (Dot1l), a histone methyltransferase that targets the histone H3 lysine 79 (H3K79), has been reported that its high expression is associated with various cancers, while the association between Dot1l expression and clear-cell renal cell carcinoma (ccRCC) is still unknown. (oncotarget.com)
  • DOT1L, the sole histone H3K79 methyltransferase , is essential for embryonic development . (bvsalud.org)
  • Our observations have broad implications for transcriptional handle for the reason that reduction of DOT1L exercise and methylated H3K79 had a negligible consequence on gene expression at significant. (micrornamimics.com)
  • To the a single hand, overexpressed leukemogenic genes in MLL rearranged cells demonstrate hypermethylation of H3K79, along with the DOT1L inhibitor EPZ004777 reverses aberrant ex pression of these genes. (micrornamimics.com)
  • These ndings assistance instructive roles for methylated H3K79 and H3K4 in illness or sure genetically engineered states. (micrornamimics.com)
  • Transient knockdown of Fh in mouse livers substantially increased monomethylation on H3K4, dimethylation on H3K9, H3K27, and H3K79, and trimethylation on H3K4. (jakenzyme.com)
  • H3K79 dimethylation has been detected in the transcribed regions of active genes. (wikipedia.org)
  • To even more substantiate the over results, we established mRNA expression of Hoxa genes whose up regulation is connected with greater H3K79 dimethylation in MLL rearranged mouse leukemia and human AML patients. (jakenzyme.com)