scholarly journals TET1 Modulates H4K16 Acetylation by Interacting with hMOF to Regulate Expression of DNA Repair Genes and Oncogenic Transformation

2015 ◽  
Author(s):  
Jianing Zhong ◽  
Xianfeng Li ◽  
Wanshi Cai ◽  
Yan Wang ◽  
Shanshan Dong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Repair ◽  
Embryonic Stem ◽  
Genomic Analysis ◽  
Dna Demethylation ◽  
Dna Repair Genes ◽  
Histone H4 ◽  
Dna Double Strand Breaks ◽  
Independent Manner ◽  
Repair Genes

The Ten Eleven Translocation 1 (TET1) protein is a DNA demethylase that regulates gene expression through alteration of DNA methylation. Recent studies have demonstrated that TET1 could modulate transcriptional expression independent of its DNA demethylation activity; however, the detailed mechanisms underlying TET1’s role in such transcriptional regulation remain not well understood. Here, we uncovered that Tet1 formed a chromatin complex with histone acetyltransferase Mof and scaffold protein Sin3a in mouse embryonic stem cells by integrative genomic analysis using publicly available ChIP-seq data sets. Specifically, the TET1/SIN3A/hMOF complex mediates acetylation of histone H4 at lysine 16, via facilitating the binding of hMOF on chromatin, to regulate expression of important DNA repair genes in DNA double strand breaks, including TP53BP1, RAD50, RAD51, and BRCA1, for homologous recombination and non-homologous end joining repairs. Under hydrogen peroxide-induced DNA damage, dissociation of TET1 and hMOF from chromatin, concurrent with increased binding of SIRT1 on chromatin, led to hypo-acetylation of H4K16, reduced expression of these DNA repair genes, and DNA repair defects in a DNA methylation independent manner. A similar epigenetic dynamic alteration was also observed in H-RASV12 oncogenic-transformed cells, supporting the notion that suppression of TET1 downregulates DNA repair genes through modifying H4K16ac, instead of its demethylation function, and therefore contribute to tumorigenesis. Taken together, our results suggested a mechanistic link between a novel TET1 complex and H4K16ac, DNA repair genes expression, and genomic instability.

scholarly journals Role of the DNA repair genes H2AX and HMGB1 in human fat distribution and lipid profiles

2020 ◽  
Vol 8 (1) ◽  
pp. e000831
Author(s):  
Kerstin Rohde ◽  
Torunn Rønningen ◽  
Lars la Cour Poulsen ◽  
Maria Keller ◽  
Matthias Blüher ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Repair ◽  
Density Lipoprotein ◽  
Fat Distribution ◽  
Lipoprotein Cholesterol ◽  
Mrna Levels ◽  
Dna Repair Genes ◽  
Specific Regulation ◽  
Repair Genes

IntroductionRegional fat distribution strongly relates to metabolic comorbidities. We identified the DNA repair genes H2AX and HMGB1 to be differentially expressed between human subcutaneous (SAT) and omental visceral adipose tissue (OVAT) depots. As increased DNA damage is linked to metabolic disease, we here sought to analyze whether depot-specific H2AX and HMGB1 expression is related to anthropometric and metabolic profiles of obesity. We further tested for different H2AX mRNA regulatory mechanisms by analyzing promoter DNA methylation and genotyped rs7350 in the H2AX locus.Research design and methodsGene expression (OVAT n=48; SAT n=55) and DNA promoter methylation data (OVAT and SAT n=77) were extracted from an existing dataset as described elsewhere. Genotype data for the 3’untranslated region (3’UTR) H2AX variant rs7350 were generated by using the TaqMan genotyping system in 243 subjects of the same cohort. Statistical analyses were done using SPSS statistics software 24 and GraphPad Prism 6.ResultsWe identified H2AX being higher (p=0.002) and HMGB1 being less expressed (p=0.0001) in OVAT compared with SAT. Further, we observed positive interdepot correlations of OVAT and SAT for both HMGB1 (p=1×10–6) and H2AX mRNA levels (p=0.024). Depot-specific associations were observed for both genes’ methylation levels with either high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides and/or with OVAT/SAT-ratio (all p<0.05). A significantly lower level of total cholesterol in minor A-Allele carriers of rs7350 compared with AG and GG carriers (p=0.001) was observed. Additionally, subjects carrying the A-allele showed lower SAT HMGB1 expression level (p=0.030).ConclusionOur results suggest a fat depot-specific regulation of H2AX and HMGB1 potentially mediated by both DNA methylation and genetic variation. Rs7350, DNA methylation and/or mRNA levels of H2AX and HMGB1 are related to lipid parameters. Further studies are warranted to evaluate the functional role of the DNA repair genes H2AX and HMGB1 in obesity and fat distribution.

scholarly journals Differential DNA Methylation in Prostate Tumors from Puerto Rican Men

2021 ◽  
Vol 22 (2) ◽  
pp. 733
Author(s):  
Gilberto Ruiz-Deya ◽  
Jaime Matta ◽  
Jarline Encarnación-Medina ◽  
Carmen Ortiz-Sanchéz ◽  
Julie Dutil ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Repair ◽  
The United States ◽  
Dna Repair Genes ◽  
Prostate Tumors ◽  
The Us ◽  
Hispanic Latinos ◽  
Methylation Patterns ◽  
Ancestry Proportions ◽  
Repair Genes

In 2020, approximately 191,930 new prostate cancer (PCa) cases are estimated in the United States (US). Hispanic/Latinos (H/L) are the second largest racial/ethnic group in the US. This study aims to assess methylation patterns between aggressive and indolent PCa including DNA repair genes along with ancestry proportions. Prostate tumors classified as aggressive (n = 11) and indolent (n = 13) on the basis of the Gleason score were collected. Tumor and adjacent normal tissue were annotated on H&E (Haemotoxylin and Eosin) slides and extracted by macro-dissection. Methylation patterns were assessed using the Illumina 850K DNA methylation platform. Raw data were processed using the Bioconductor package. Global ancestry proportions were estimated using ADMIXTURE (k = 3). One hundred eight genes including AOX1 were differentially methylated in tumor samples. Regarding the PCa aggressiveness, six hypermethylated genes (RREB1, FAM71F2, JMJD1C, COL5A3, RAE1, and GABRQ) and 11 hypomethylated genes (COL9A2, FAM179A, SLC17A2, PDE10A, PLEKHS1, TNNI2, OR51A4, RNF169, SPNS2, ADAMTSL5, and CYP4F12) were identified. Two significant differentially methylated DNA repair genes, JMJD1C and RNF169, were found. Ancestry proportion results for African, European, and Indigenous American were 24.1%, 64.2%, and 11.7%, respectively. The identification of DNA methylation patterns related to PCa in H/L men along with specific patterns related to aggressiveness and DNA repair constitutes a pivotal effort for the understanding of PCa in this population.

scholarly journals Limited DNA repair gene repertoire in Ascomycete yeast revealed by comparative genomics

2019 ◽  
Author(s):  
Shira Milo ◽  
Reut Harari Misgav ◽  
Einat Hazkani-Covo ◽  
Shay Covo
Keyword(s):  
Dna Repair ◽  
Genome Evolution ◽  
Genomic Analysis ◽  
Comparative Genomic ◽  
Gene Repertoire ◽  
Dna Repair Genes ◽  
Repair Gene ◽  
Brettanomyces Bruxellensis ◽  
Dna Repair Gene ◽  
Repair Genes

Abstract Ascomycota is the largest phylogenetic group of fungi that includes species important to human health and wellbeing. DNA repair is important for fungal survival and genome evolution. Here, we describe a detailed comparative genomic analysis of DNA repair genes in Ascomycota. We determined the DNA repair gene repertoire in Taphrinomycotina, Saccharomycotina, Leotiomycetes, Sordariomycetes, Dothideomycetes, and Eurotiomycetes. The subphyla of yeasts, Saccharomycotina and Taphrinomycotina, have a smaller DNA repair gene repertoire comparing to Pezizomycotina. Some genes were absent from most, if not all, yeast species. To study the conservation of these genes in Pezizomycotina, we used the GLOOME algorithm that provides the expectations of gain or loss of genes given the tree topology. Genes that were absent from most of the species of Taphrinomycotina or Saccharomycotina showed lower conservation in Pezizomycotina. This suggests that the absence of some DNA repair in yeasts is not random; genes with a tendency to be lost in other classes are missing. We ranked the conservation of DNA repair genes in Ascomycota. We found that Rad51 and its paralogs were less conserved than other recombinational proteins, suggesting that there is a redundancy between Rad51 and its paralogs, at least in some species. Finally, based on the repertoire of UV repair genes, we found conditions that differentially kill the wine pathogen Brettanomyces bruxellensis and not Saccharomyces cerevisiae. In summary, our analysis provides testable hypotheses to the role of DNA repair proteins in the genome evolution of Ascomycota.

scholarly journals Aberrant DNA methylation status of DNA repair genes in breast cancer treated with neoadjuvant chemotherapy

2013 ◽  
Vol 18 (12) ◽  
pp. 1120-1130 ◽  
Author(s):  
Yoshiyuki Watanabe ◽  
Ichiro Maeda ◽  
Ritsuko Oikawa ◽  
Wenwen Wu ◽  
Kyoko Tsuchiya ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Dna Repair ◽  
Neoadjuvant Chemotherapy ◽  
Methylation Status ◽  
Dna Repair Genes ◽  
Aberrant Dna Methylation ◽  
Repair Genes

scholarly journals Genomic analysis of DNA repair genes and androgen signaling in prostate cancer

BMC Cancer ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Kasey Jividen ◽  
Katarzyna Z Kedzierska ◽  
Chun-Song Yang ◽  
Karol Szlachta ◽  
Aakrosh Ratan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Genomic Analysis ◽  
Dna Repair Genes ◽  
Repair Genes

Truncating variants in DNA-repair genes and their effect on AAO of hereditary breast cancer

2018 ◽  
Author(s):  
I Sepahi ◽  
U Faust ◽  
M Sturm ◽  
K Bosse ◽  
M Kehrer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Hereditary Breast Cancer ◽  
Dna Repair Genes ◽  
Repair Genes
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