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Biomedical subjects

John Boyle

Publications and source records attributed to John Boyle.

4 recordsLinked to original sources

Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.

Posttranslational histone modifications participate in modulating the structure and function of chromatin. Promoters of transcribed genes are enriched with K4 trimethylation and hyperacetylation on the N-terminal tail of histone H3. Recently, PHD finger proteins, like Yng1 in the NuA3 HAT complex, were shown to interact with H3K4me3, indicating a biochemical link between K4 methylation and hyperacetylation. By using a combination of mass spectrometry, biochemistry, and NMR, we detail the Yng1 PHD-H3K4me3 interaction and the importance of NuA3-dependent acetylation at K14. Furthermore, genome-wide ChIP-Chip analysis demonstrates colocalization of Yng1 and H3K4me3 in vivo. Disrupting the K4me3 binding of Yng1 altered K14ac and transcription at certain genes, thereby demonstrating direct in vivo evidence of sequential trimethyl binding, acetyltransferase activity, and gene regulation by NuA3. Our data support a general mechanism of transcriptional control through which histone acetylation upstream of gene activation is promoted partially through availability of H3K4me3, "read" by binding modules in select subunits.

Chromatin Immunoprecipitation↗

Gene-Expression Omnibus integration and clustering tools in SeqExpress.

UNLABELLED: SeqExpress, a gene-expression analysis suite, has been extended to offer a number of cluster generation, refinement and visualization techniques. The cluster generation methods have been specialized to deal with aspects of the sparseness and extreme values that occur within microarray data. The results of such cluster analysis can then be refined using either: a functional enrichment based procedure, which examines each cluster to see if it possesses an unusually high or low concentration of ontology terms; or by using Expectation-Maximization to find a mixture of model based distributions within the datasets. Visualizations are provided both to explore and compare the results of the cluster generation algorithms. In addition, a tool has been developed which integrates SeqExpress with the Gene-Expression Omnibus repository. The tool provides seamless access to the large number of experimental results in the repository, so that they can be visualized and analysed locally using SeqExpress. AVAILABILITY: SeqExpress is available as a 6 MB download from http://www.seqexpress.com and runs under Windows. A server-based version is available and is required for the GEO integration. SeqExpress is not affiliated with any academic institution, funding body or commercial organization and is free to use by all.

Algorithms↗

SeqExpress: desktop analysis and visualization tool for gene expression experiments.

SUMMARY: SeqExpress is a stand-alone desktop application for the identification of relevant genes within collections of microarray or SAGE experiments. A number of analysis, filtering and visualization tools are provided to aid in the selection of groups of genes. If R is installed then the application can use this to provide further analysis. AVAILABILITY: SeqExpress is available at: http://www.seqexpress.com

Algorithms↗

Utility of the Rome I and Rome II criteria for irritable bowel syndrome in U.S. women.

OBJECTIVES: Using interview data from a large, community-based sample of American women, we assessed the lifetime prevalence of irritable bowel syndrome (IBS) using questions consistent with the Rome II criteria, determined the sensitivity of Rome I and II in women diagnosed with IBS by their community physician, and identified whether there are differences in the patients identified by Rome I versus II. METHODS: A geographically diverse national probability sample of women diagnosed with IBS was identified and interviewed by telephone screening of a national, random digit dialing sample of households. A parallel national survey of adult females was conducted to determine the lifetime prevalence of IBS in U.S. women. Screening and interviews were conducted by experienced, female interviewers. IBS was defined by variations on the Rome I/II criteria. RESULTS: In the national community sample, lifetime IBS prevalence was 5.4% using Rome II. Full interviews were completed in 1,014 IBS patients. In the IBS sample, Rome I was significantly more sensitive than Rome II (84% vs 49%, p < 0.001). There was 47% agreement between Rome I and II. Of patients with IBS by Rome I, 58% met Rome II. Only 17.7% did not meet either Rome I or II. CONCLUSIONS: Rome I was more sensitive than Rome II in this community sample of female IBS patients. Rome I/II do not necessarily identify the same IBS patients. These findings have important implications for clinical research in IBS patients and raise questions about whether the Rome II criteria are sensitive enough to be useful in clinical practice.

Adult↗