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Brian D Dynlacht

Publications and source records attributed to Brian D Dynlacht.

4 recordsLinked to original sources

Functional genomics via multiscale analysis: application to gene expression and ChIP-on-chip data.

UNLABELLED: We present a fast, versatile and adaptive-multiscale algorithm for analyzing a wide-variety of DNA microarray data. Its primary application is in normalization of array data as well as subsequent identification of 'enriched targets', e.g. differentially expressed genes in expression profiling arrays and enriched sites in ChIP-on-chip experimental data. We show how to accommodate the unique characteristics of ChIP-on-chip data, where the set of 'enriched targets' is large, asymmetric and whose proportion to the whole data varies locally. SUPPLEMENTARY INFORMATION: Supplementary figures, related preprint, free software as well as our raw DNA microarray data with PCR validations are available at http://www.math.umn.edu/~lerman/supp/bioinfo06 as well as Bioinformatics online.

Algorithms↗

Devising transcriptional regulatory networks operating during the cell cycle and differentiation using ChIP-on-chip.

The study of global transcriptional regulatory networks in eukaryotes has advanced rapidly in the last five years with the advent of genomic microarrays that allow investigators to comprehensively scrutinize the structure and composition of transcriptomes and chromatin. Many facets of this field have benefited from an examination of the location of proteins associated with chromatin. We describe here how we have used genomic arrays to perform location analysis (or ChIP-on-chip analysis) of regulatory factors that control the complex process of cell cycle progression and differentiation, in order to identify key direct transcriptional targets. Combining this information with data obtained through expression profiling and computational analysis of transcription factor binding sites has also allowed us to devise transcriptional regulatory networks governing these processes.

Animals↗

Highly specific interactions between bHLH transcription factors and chromatin during retina development.

Basic helix-loop-helix (bHLH) transcription factors such as atonal homolog 5 (ATH5) and neurogenin 2 (NGN2) determine crucial events in retinogenesis. Using chromatin immunoprecipitation, we demonstrate that their interactions with target promoters undergo dynamic changes as development proceeds in the chick embryo. Chick ATH5 associates with its own promoter and with the promoter of the beta3 nicotinic receptor specifically in retinal ganglion cells and their precursors. NGN2 binds to the ATH5 promoter in retina but not in optic tectum, suggesting that interactions between bHLH factors and chromatin are highly tissue specific. The transcriptional activations of both promoters correlate with dimethylation of lysine 4 on histone H3. Inactivation of the ATH5 promoter in differentiated neurons is accompanied by replication-independent chromatin de-methylation. This report is one of the first demonstrations of correlation between gene expression, binding of transcription factors and chromatin modification in a developing neural tissue.

Animals↗