Dataset Information

Strand bias structure in mouse DNA gives a glimpse of how chromatin structure affects gene expression.

ABSTRACT:

Background

On a single strand of genomic DNA the number of As is usually about equal to the number of Ts (and similarly for Gs and Cs), but deviations have been noted for transcribed regions and origins of replication.

Results

The mouse genome is shown to have a segmented structure defined by strand bias. Transcription is known to cause a strand bias and numerous analyses are presented to show that the strand bias in question is not caused by transcription. However, these strand bias segments influence the position of genes and their unspliced length. The position of genes within the strand bias structure affects the probability that a gene is switched on and its expression level. Transcription has a highly directional flow within this structure and the peak volume of transcription is around 20 kb from the A-rich/T-rich segment boundary on the T-rich side, directed away from the boundary. The A-rich/T-rich boundaries are SATB1 binding regions, whereas the T-rich/A-rich boundary regions are not.

Conclusion

The direct cause of the strand bias structure may be DNA replication. The strand bias segments represent a further biological feature, the chromatin structure, which in turn influences the ease of transcription.

SUBMITTER: Evans KJ

PROVIDER: S-EPMC2266913 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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Publications

Strand bias structure in mouse DNA gives a glimpse of how chromatin structure affects gene expression.

Evans Kenneth J KJ

BMC genomics 20080114

<h4>Background</h4>On a single strand of genomic DNA the number of As is usually about equal to the number of Ts (and similarly for Gs and Cs), but deviations have been noted for transcribed regions and origins of replication.<h4>Results</h4>The mouse genome is shown to have a segmented structure defined by strand bias. Transcription is known to cause a strand bias and numerous analyses are presented to show that the strand bias in question is not caused by transcription. However, these strand b ...[more]

PMID: 18194530

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Project description:The activity of DNA adenine methyltransferase (Dam) and DNA cytosine methyltransferase (Dcm) together account for nearly all methylated nucleotides in the Escherichia coli K-12 MG1655 genome. Previous studies have shown that perturbation of DNA methylation alters E. coli global gene expression, but it is unclear whether the methylation state of Dam or Dcm target sites regulates local transcription. In recent genome-wide experiments, we observed an underrepresentation of Dam sites in transcriptionally silent extended protein occupancy domains (EPODs), prompting us to hypothesize that EPOD formation is caused partially by low Dam site density. We thus hypothesized that a methylation-deficient version of MG1655 would show large-scale aberrations in chromatin structure. To test our hypothesis, we cloned methyltransferase deletion strains and performed global protein occupancy profiling using high resolution in vivo protein occupancy display (IPOD-HR), chromatin immunoprecipitation for RNA polymerase (RNAP-ChIP), and transcriptome abundance profiling using RNASeq. Our results indicate that loss of DNA methylation does not result in large-scale changes in genomic protein occupancy such as the formation of EPODs, indicating that the previously observed depletion of Dam sites in EPODs is correlative, rather than causal, in nature. However, loci with dense clustering of Dam methylation sites show methylation-dependent changes in local RNA polymerase and total protein occupancy, but local transcription is unaffected. Our transcriptome profiling data indicates that deletion of dam and/or dcm results in significant expression changes within some functional gene categories including SOS response, flagellar synthesis, and translation, but these expression changes appear to result from indirect regulatory consequences of methyltransferase deletion. In agreement with the downregulation of genes involved in flagellar synthesis, dam deletion is characterized by a swimming motility-deficient phenotype. We conclude that DNA methylation does not control the overall protein occupancy landscape of the E. coli genome, and that observable changes in gene regulation are generally not resulting from regulatory consequences of local methylation state.

Dataset Information

Strand bias structure in mouse DNA gives a glimpse of how chromatin structure affects gene expression.

Background

Results

Conclusion

Publications

Strand bias structure in mouse DNA gives a glimpse of how chromatin structure affects gene expression.

Similar Datasets

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