LATE-REPLICATING HETEROCHROMATIN IS CHARACTERISED BY DECREASED CYTOSINE METHYLATION IN THE HUMAN GENOME
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: John Greally
PROVIDER: E-GEOD-27538 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Heterochromatin is believed to be associated with increased levels of cytosine methylation. With the recent availability of genome-wide, high-resolution molecular data reflecting cytosine methylation or heterochromatic organization, such relationships can be explored systematically. As a well-defined surrogate for heterochromatin, we tested the relationship between DNA replication timing and cytosine methylation in two human cell types, unexpectedly finding that the later-replicating, more heterochromatic regions to be less methylated than early-replicating regions. When we integrated gene expression data into the study, we found that regions of increased gene expression were earlier replicating, as previously identified, and that transcription-targeted cytosine methylation (TTCM) in gene bodies accounts for the positive correlation with early replication. A Self-Organising Map (SOM) approach was able to identify genomic regions with early replication and increased methylation but lacking annotated transcripts, which would have been missed in simple two variable analyses and may encode unrecognized intergenic transcripts. We conclude that the relationship of cytosine methylation with heterochromatin is not simple, and depends on whether the genomic context is tandemly-repetitive sequences often found near centromeres, which are known to be heterochromatic and methylated, or the remaining majority of the genome, where cytosine methylation is targeted preferentially to the transcriptionally-active, euchromatic compartment of the genome.
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Project description:LATE-REPLICATING HETEROCHROMATIN IS CHARACTERISED BY DECREASED CYTOSINE METHYLATION IN THE HUMAN GENOME (HELP assay)
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