RICHARD A contact YOUNG

..RAR is thought to bind the genome constitutively, and only induce transcription in the presence of the retinoid ligand. However, little is known about where RAR binds to the genome or how it selects target sites...

..Recent evidence with comparing multiple technologies suggests that expanding these datasets using different platforms would be a useful resource for examining the mechanisms underlying pluripotency regulation...

..This approach will allow investigators to determine the genomic binding locations of DNA interacting proteins during development and expedite the assembly of the genetic networks that regulate embryogenesis...

..These studies have, as a consequence, uncovered fundamental mechanisms that control mammalian gene expression, connect gene expression to chromosome structure, and contribute to human disease...

..Our results reveal that eukaryotic cellular functions are highly connected through networks of transcriptional regulators that regulate other transcriptional regulators...

..The ability to detect this interaction of signaling kinases with target genes can be used to more precisely and comprehensively map the regulatory circuitry that eukaryotic cells use to respond to their environment...

..We also present a genome-wide location analysis data set for regulators in yeast cells treated with rapamycin, and use the GRAM algorithm to provide biological insights into this regulatory network..

..Our results suggest how misregulation of HNF4alpha can contribute to type 2 diabetes...

..The ability of MLL1 to serve as a start site-specific global transcriptional regulator and to participate in larger chromatin domains at the Hox genes reveals dual roles for MLL1 in maintenance of cellular identity...

..These maps provide the foundation for further understanding the roles of chromatin in gene expression and genome maintenance...

..We find that environment-specific use of regulatory elements predicts mechanistic models for the function of a large population of yeast's transcriptional regulators...

..These results provide new insights into the transcriptional regulation of stem cells and reveal how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal...

..In all the cases the identified motifs are consistent with the published data with regard to the binding specificity of the proteins...

..Program-specific distribution across the genome may be a general mechanism by which transcription factors regulate distinct gene expression programs in response to signaling...

..The recent description of the genetic network controlling the cell cycle illustrates the tremendous potential of these approaches for deciphering gene expression regulatory networks in eukaryotic cells...

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..These results suggest a revised model for transcription initiation and elongation apparatuses in living cells...

..The resulting noise model includes novel features such as heavy-tailed additive noise and a gene-specific bias term. We also verify that the resulting noise and prior models fit data from an Affymetrix human chip set...

..We present results on the yeast transcription factors Gcn4 and Mig2 to demonstrate JBD's spatial resolution capabilities and show that positional priors allow computational discovery of the Mig2 motif when a standard approach fails...

..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...

..Our results suggest that the Wnt pathway, through Tcf3, brings developmental signals directly to the core regulatory circuitry of ES cells to influence the balance between pluripotency and differentiation...

..Our results identify the portions of chromosomes where cohesins are protected from removal during meiosis I and show that kinetochore components and cohesins themselves are required to establish this cohesin protective domain...

..These observations extend to differentiated cells, suggesting that transcription initiation at most genes is a general phenomenon in human cells...

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..Overall, the results indicate that this Hsfp can activate DC independently of LPS but still requires Tlr4 for an optimal CD8 T cell response...

..This distinct TLR4 response may provide the basis to diagnose clinical Gram-negative infections...

..Our studies reveal portions of the core circuitry of human hepatocytes...

..Thus, the ChIP-chip data uncover a much larger than expected regulatory network, which integrates diverse patterning processes during development...

..These protocols require approximately 1 week to complete once sufficient numbers of cells have been obtained, and have been used to produce robust, high-quality ChIP-chip results in many different cell and tissue types...

..These data reveal how key ES cell transcription factors promote the ES cell miRNA expression program and integrate miRNAs into the regulatory circuitry controlling ES cell identity...

..These results suggest that divergent transcription over short distances is common for active promoters and may help promoter regions maintain a state poised for subsequent regulation...

..We discuss the implications of these results for the role of c-Myc amplification in human cancer...

..Our data indicate that E2F directly links cell cycle progression with the coordinate regulation of genes essential for both the synthesis of DNA as well as its surveillance...

..Foxp3 suppression of its targets appears to be crucial for the normal function of T(reg) cells, because overactive variants of some target genes are known to be associated with autoimmune disease...

..The specific molecular design employed in the synthesis of ATFs may lead to the development of novel gene-targeting pharmaceuticals for treatment of fatal and chronic diseases...

..Mediator and cohesin co-occupy different promoters in different cells, thus generating cell-type-specific DNA loops linked to the gene expression program of each cell...

..Thus, H2AZ, together with PcG proteins, may establish specialized chromatin states in ES cells necessary for the proper execution of developmental gene expression programs...

..This study identifies NF-kappaB target genes, reveals how the different NF-kappaB proteins coordinate their activity, and provides an initial map of the transcriptional regulatory network that underlies the host response to infection...

..We propose that Pol II stalling facilitates rapid temporal and spatial changes in gene activity during development...

..These results improve our understanding of macrophage defenses, provide insights into mechanisms of pathogenesis, and suggest targets for therapeutic intervention...

..These genes are subjected to repression by both Polycomb group proteins and SetDB1, and loss of either regulator can destabilize ES cell state...

..Although some variation in chromatin structure and gene expression was observed in these cell lines, these variations did not serve to distinguish ESCs from iPSCs...

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..We conclude that, during differentiation, RBP2 exerts inhibitory effects on multiple genes through direct interaction with their promoters...

..Collectively, our results confirm and extend the proposal that individual TAFs have selective transcriptional roles and distinct functions...

..The interaction evidently positions each activator, as it activates transcription, so that it gets phosphorylated by SRB10, and thus a common mechanism targets disparate substrates to the kinase...

..Therefore, the role of Myog in mediating terminal differentiation is, in part, to enhance expression of a subset of genes previously initiated by Myod...

..Our results illustrate the response of a chromatin-remodeling factor to signaling cascades and suggest that changes in the activity of chromatin-remodeling factors are reflected in changes in their localization in the genome...

..These results indicate that CREB phosphorylation alone is not a reliable predictor of target gene activation and that additional CREB regulatory partners are required for recruitment of the transcriptional apparatus to the promoter...

..Similar PBM experiments should be useful in identifying new cis regulatory elements and transcriptional regulatory networks in various genomes...

..Therefore, the RSC complex is generally recruited to Pol III promoters and it is specifically recruited to Pol II promoters by transcriptional activators and repressors...

..Our results indicate that TAL1 may act as a bifunctional transcriptional regulator (activator and repressor) at the top of a complex regulatory network that disrupts normal T-cell homeostasis and contributes to leukemogenesis...

..In addition, many are already repressed in normal cells. These results are consistent with the hypothesis that cancer-related de novo methylation may come about through an instructive mechanism...

..Thus, the regulatory mechanisms maintaining quiescence are robust even to complete loss of conserved transcription factor binding events...

..These results identify c-MYC as an essential mediator of NOTCH1 signaling and integrate NOTCH1 activation with oncogenic signaling pathways upstream of c-MYC...

..Our results suggest that promotion of differentiation by pRB involves neutralization of free RBP2 and transcriptional activation of RBP2 targets linked to euchromatin maintenance...

..These results show that HIV-1 Tat reprograms host dendritic cell gene expression to facilitate expansion of HIV-1 infection...

..Manipulating the epigenomic state and examining the results on tumorigenicity would provide direct insight on how these signatures translate into clinically relevant phenotypes. ..

..Consequently, this meeting should be uniquely important for graduate students, postdocs and other researchers who future careers will involve these interdisciplinary efforts. ..

..The health relatedness of this project devices from its contribution to the understanding of the fundamental mechanisms that control gene expression. ..

..Norman Letvin (Subcontract with Beth Israel Deaconess Medical Center), and for protection against a live challenge with SIV in collaboration with Dr. Michael Wyand (Subcontract with GTC Mason Laboratories). ..

..cerevisiae using biochemical approaches, 4) to study the transcriptional functions of the TBP-binding proteins using wild-type and mutant proteins in transcription systems in vitro. ..

..Embryonic stem cells hold enormous potential for diverse medical applications and improved understanding of regulatory circuitry from these studies should facilitate efforts to manipulate cell fates for regenerative medicine. ..

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..Dr. Bell's laboratory will provide knowledge in beta-cell biology and expertise in isolating mouse islets and culturing beta-cell lines. ..

..The health relatedness of this project derives from its contribution to the understanding of basic molecular mechanisms that control gene expression. ..

..The health relatedness of this research derives from its contribution to the understanding of the basic molecular mechanisms that control gene expression...

..The health relatedness of this project derives from its contribution to the understanding of the basic molecular mechanisms which control gene expression...

..The health relatedness of this project derives from its contribution to the understanding of basic molecular mechanisms that control gene expression...