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Status |
Public on Jun 06, 2013 |
Title |
H3K79 methylation - cell cycle |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing Methylation profiling by high throughput sequencing
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Summary |
Mammalian DNA replication starts at distinct chromosomal sites in a tissue-specific pattern coordinated with transcription, but previous studies have not yet identified a chromatin modification that correlates with the initiation of DNA replication. This submission is associated with a paper in which we report that replication initiation events are associated with a high frequency of methylation of histone H3 on lysine K79 (H3K79Me2 and H3K79Me3). H3K79Me2-containing chromatin exhibited the highest enrichment of replication initiation events observed in a single chromatin modification. Importantly, H3K79 methylation was enriched in chromatin containing a replicator (a DNA sequence capable of initiating DNA replication), but not in chromatin containing a mutant replicator that could not initiate replication. The association of H3K79Me2 with replication initiation sites was independent and not synergistic with other chromatin modifications. H3K79 methylation exhibited a wider distribution and greater abundance during S-phase, but regions of chromatin that were only modified during S-phase were not enriched in replication initiation events. In addition, the paper shows that depletion of DOT1L, the sole enzyme responsible for H3K79 methylation, triggered limited genomic over-replication. These data are consistent with the hypothesis that methylation of H3K79 associates with replication origins and marks replicated chromatin during S-phase to prevent re-replication and preserve genomic stability.
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Overall design |
Evaluation of HeK79 methylation in chromatin samples from cell cycle fractionated K562 leukemia cells. Unsyncrhonized untreated cultures of K562 cells were fractionated by size using centrifugal elutriation. Chromatin was isolated and subject to ChIP-Seq with antibodies directed against dimethylated and trimethylated lysine on histone H3.
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Contributor(s) |
Aladjem MI, Zhao K |
Citation(s) |
23754963 |
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Submission date |
Jan 24, 2012 |
Last update date |
May 15, 2019 |
Contact name |
Mirit I Aladjem |
E-mail(s) |
aladjemm@mail.nih.gov
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Phone |
301-435-2848
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Organization name |
National Cancer Institute
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Department |
DNA Replication Group
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Street address |
37 Convent Dr. Building 37, Room 5068D
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City |
Bethesda |
State/province |
MD |
ZIP/Postal code |
20892 |
Country |
USA |
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Platforms (1) |
GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
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Samples (11)
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Relations |
SRA |
SRP010482 |
BioProject |
PRJNA151597 |