Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA135285 | ENA |
REPOSITORIES: ENA
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Project description:DNA methylation is a central epigenetic modification that has essential roles in cellular processes including chromatin structure, gene regulation, development and disease. The de novo DNA methyltransferases are responsible for the generation of genomic methylation patterns, but the underlying mechanisms are still poorly understood. Here, we show that phosphorylation of DNMT3A by the CK2 protein kinase regulates the establishment of DNA methylation patterns. We find that DNMT3A is phosphorylated by CK2 at two key residues located near its PWWP domain. We observed that, through phosphorylation of these residues, CK2 negatively regulates DNMT3AM-bM-^@M-^Ys ability to methylate DNA and consistent with this, CK2 was found to decrease overall genomic level of 5-methylcytosine. Further, genome-wide DNA methylation analysis in CK2-depleted cells revealed that CK2 affects primarily CpG methylation of several heterochromatin repeats as well as Alu elements. Along these lines, we found that CK2-mediated phosphorylation of DNMT3A was required for its proper heterochromatin localization. Our results define phosphorylation as a new mode of regulation of de novo DNA methyltransferase function. These findings further uncover a previously unrecognized mechanism for the regulation of methylation at repetitive elements. They shed new light into the origin of DNA methylation patterns. Bisulphite converted DNA from 6 samples were hybridised to the Illumina Infinium 27K Human Methylation Beadchip v1.2
2014-07-17 | E-GEOD-26164 | biostudies-arrayexpress
Project description:Regulation of DNA methylation by CK2-mediated phosphorylation of DNMT3A (Methyl-Seq)
| PRJNA135895 | ENA
Project description:DNA methylation is a central epigenetic modification that has essential roles in cellular processes including chromatin structure, gene regulation, development and disease. The de novo DNA methyltransferases are responsible for the generation of genomic methylation patterns, but the underlying mechanisms are still poorly understood. Here, we show that phosphorylation of DNMT3A by the CK2 protein kinase regulates the establishment of DNA methylation patterns. We find that DNMT3A is phosphorylated by CK2 at two key residues located near its PWWP domain. We observed that, through phosphorylation of these residues, CK2 negatively regulates DNMT3A’s ability to methylate DNA and consistent with this, CK2 was found to decrease overall genomic level of 5-methylcytosine. Further, genome-wide DNA methylation analysis in CK2-depleted cells revealed that CK2 affects primarily CpG methylation of several heterochromatin repeats as well as Alu elements. Along these lines, we found that CK2-mediated phosphorylation of DNMT3A was required for its proper heterochromatin localization. Our results define phosphorylation as a new mode of regulation of de novo DNA methyltransferase function. These findings further uncover a previously unrecognized mechanism for the regulation of methylation at repetitive elements. They shed new light into the origin of DNA methylation patterns.
2014-07-17 | GSE26810 | GEO
Project description:DNA methylation is a central epigenetic modification that has essential roles in cellular processes including chromatin structure, gene regulation, development and disease. The de novo DNA methyltransferases are responsible for the generation of genomic methylation patterns, but the underlying mechanisms are still poorly understood. Here, we show that phosphorylation of DNMT3A by the CK2 protein kinase regulates the establishment of DNA methylation patterns. We find that DNMT3A is phosphorylated by CK2 at two key residues located near its PWWP domain. We observed that, through phosphorylation of these residues, CK2 negatively regulates DNMT3A’s ability to methylate DNA and consistent with this, CK2 was found to decrease overall genomic level of 5-methylcytosine. Further, genome-wide DNA methylation analysis in CK2-depleted cells revealed that CK2 affects primarily CpG methylation of several heterochromatin repeats as well as Alu elements. Along these lines, we found that CK2-mediated phosphorylation of DNMT3A was required for its proper heterochromatin localization. Our results define phosphorylation as a new mode of regulation of de novo DNA methyltransferase function. These findings further uncover a previously unrecognized mechanism for the regulation of methylation at repetitive elements. They shed new light into the origin of DNA methylation patterns.
2014-07-17 | GSE26164 | GEO
Project description:Structural basis for DNMT3A-mediated de novo DNA methylation (HumanMethylation450 BeadChip)
| PRJNA362209 | ENA
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
2011-08-25 | GSE23936 | GEO
Project description:Genome-scale DNA methylation profiling using the Infinium DNA methylation BeadChip platform and samples from acute myeloid leukemia patients screened for their mutation status of DNMT3a, a frequent aberration in AML.
2015-10-07 | GSE62298 | GEO
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs. Two-condition experiment, KP MSCs vs. 3A6 MSCs.
2011-08-24 | E-GEOD-23936 | biostudies-arrayexpress
Project description:Genome-wide parent-of-origin DNA methylation analysis [Methylation450 BeadChip]
| PRJNA229408 | ENA
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature