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Biomedical subjects

Thomas L Volkert

Publications and source records attributed to Thomas L Volkert.

4 recordsLinked to original sources

Control of developmental regulators by Polycomb in human embryonic stem cells.

Polycomb group proteins are essential for early development in metazoans, but their contributions to human development are not well understood. We have mapped the Polycomb Repressive Complex 2 (PRC2) subunit SUZ12 across the entire nonrepeat portion of the genome in human embryonic stem (ES) cells. We found that SUZ12 is distributed across large portions of over two hundred genes encoding key developmental regulators. These genes are occupied by nucleosomes trimethylated at histone H3K27, are transcriptionally repressed, and contain some of the most highly conserved noncoding elements in the genome. We found that PRC2 target genes are preferentially activated during ES cell differentiation and that the ES cell regulators OCT4, SOX2, and NANOG cooccupy a significant subset of these genes. These results indicate that PRC2 occupies a special set of developmental genes in ES cells that must be repressed to maintain pluripotency and that are poised for activation during ES cell differentiation.

Animals↗

Program-specific distribution of a transcription factor dependent on partner transcription factor and MAPK signaling.

Specialized gene expression programs are induced by signaling pathways that act on transcription factors. Whether these transcription factors can function in multiple developmental programs through a global switch in promoter selection is not known. We have used genome-wide location analysis to show that the yeast Ste12 transcription factor, which regulates mating and filamentous growth, is bound to distinct program-specific target genes dependent on the developmental condition. This condition-dependent distribution of Ste12 requires concurrent binding of the transcription factor Tec1 during filamentation and is differentially regulated by the MAP kinases Fus3 and Kss1. Program-specific distribution across the genome may be a general mechanism by which transcription factors regulate distinct gene expression programs in response to signaling.

DNA-Binding Proteins↗

Transcriptional regulatory networks in Saccharomyces cerevisiae.

We have determined how most of the transcriptional regulators encoded in the eukaryote Saccharomyces cerevisiae associate with genes across the genome in living cells. Just as maps of metabolic networks describe the potential pathways that may be used by a cell to accomplish metabolic processes, this network of regulator-gene interactions describes potential pathways yeast cells can use to regulate global gene expression programs. We use this information to identify network motifs, the simplest units of network architecture, and demonstrate that an automated process can use motifs to assemble a transcriptional regulatory network structure. Our results reveal that eukaryotic cellular functions are highly connected through networks of transcriptional regulators that regulate other transcriptional regulators.

Algorithms↗

Two transcripts, differing at their 3' ends, are produced from the Candida albicans SEC14 gene.

A search for Candida albicans mutants defective in filamentous growth led to the isolation of a mutant strain with an insertion mutation in the SEC14 gene. SEC14 encodes the phosphatidylinositol/phosphatidylcholine transfer protein, an essential protein in the yeast Saccharomyces cerevisiae. In the dimorphic yeast Yarrowia lipolytica, SEC14 is needed for growth only in the hyphal form and is not required for growth in the yeast form. However, unlike Y. lipolytica SEC14, C. albicans SEC14 is probably essential for growth. Northern blot analysis and PCR amplification of transcripts produced from the SEC14 gene demonstrated that two transcripts differing at their 3' ends were produced. The two transcripts may regulate the activity of SEC14 so that Sec14p can perform two functions in C. albicans. One function may be an essential function analogous to the function of Sec14p in S. cerevisiae and the second function may be important during filamentous growth, analogous to the function of Sec14p in Y. lipolytica.

Amino Acid Sequence↗