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Bender, Welcome

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Bender, Welcome
Author's Publications: search.filters.isAuthorOfPublication.84b0385c-3596-49d2-8a00-9351692d1455

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Now showing 1 - 4 of 4
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    H3K27 modifications define segmental regulatory domains in the Drosophila bithorax complex
    (eLife Sciences Publications, Ltd, 2014) Bowman, Sarah K.; Deaton, Aimee; Domingues, Heber; Wang, Peggy I; Sadreyev, Ruslan; Kingston, Robert; Bender, Welcome
    The bithorax complex (BX-C) in Drosophila melanogaster is a cluster of homeotic genes that determine body segment identity. Expression of these genes is governed by cis-regulatory domains, one for each parasegment. Stable repression of these domains depends on Polycomb Group (PcG) functions, which include trimethylation of lysine 27 of histone H3 (H3K27me3). To search for parasegment-specific signatures that reflect PcG function, chromatin from single parasegments was isolated and profiled. The H3K27me3 profiles across the BX-C in successive parasegments showed a ‘stairstep’ pattern that revealed sharp boundaries of the BX-C regulatory domains. Acetylated H3K27 was broadly enriched across active domains, in a pattern complementary to H3K27me3. The CCCTC-binding protein (CTCF) bound the borders between H3K27 modification domains; it was retained even in parasegments where adjacent domains lack H3K27me3. These findings provide a molecular definition of the homeotic domains, and implicate precisely positioned H3K27 modifications as a central determinant of segment identity. DOI: http://dx.doi.org/10.7554/eLife.02833.001
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    abd-A Regulation by the iab-8 Noncoding RNA
    (Public Library of Science, 2012) Gummalla, Maheshwar; Maeda, Robert K.; Castro Alvarez, Javier J.; Gyurkovics, Henrik; Singari, Swetha; Edwards, Kevin A.; Karch, François; Bender, Welcome
    The homeotic genes in Drosophila melanogaster are aligned on the chromosome in the order of the body segments that they affect. The genes affecting the more posterior segments repress the more anterior genes. This posterior dominance rule must be qualified in the case of abdominal-A (abd-A) repression by Abdominal-B (Abd-B). Animals lacking Abd-B show ectopic expression of abd-A in the epidermis of the eighth abdominal segment, but not in the central nervous system. Repression in these neuronal cells is accomplished by a 92 kb noncoding RNA. This “iab-8 RNA” produces a micro RNA to repress abd-A, but also has a second, redundant repression mechanism that acts only “in cis.” Transcriptional interference with the abd-A promoter is the most likely mechanism.
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    The structure of Polycomb-repressed chromatin in the bithorax complex
    (BioMed Central, 2013) Bowman, Sarah K.; Deaton, Aimee; Domingues, Heber; Bender, Welcome; Kingston, Robert
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    Functional Evolution of cis-Regulatory Modules at a Homeotic Gene in Drosophila
    (Public Library of Science, 2009) Ho, Margaret C. W.; Goetz, Sara E.; Schiller, Benjamin J.; Bae, Esther; Tran, Diana A.; Shur, Andrey S.; Rau, Christoph; Celniker, Susan E.; Drewell, Robert A.; Johnsen, Holly; Allen, John M; Bender, Welcome; Fisher, William W.
    It is a long-held belief in evolutionary biology that the rate of molecular evolution for a given DNA sequence is inversely related to the level of functional constraint. This belief holds true for the protein-coding homeotic (Hox) genes originally discovered in Drosophila melanogaster. Expression of the Hox genes in Drosophila embryos is essential for body patterning and is controlled by an extensive array of cis-regulatory modules (CRMs). How the regulatory modules functionally evolve in different species is not clear. A comparison of the CRMs for the Abdominal-B gene from different Drosophila species reveals relatively low levels of overall sequence conservation. However, embryonic enhancer CRMs from other Drosophila species direct transgenic reporter gene expression in the same spatial and temporal patterns during development as their D. melanogaster orthologs. Bioinformatic analysis reveals the presence of short conserved sequences within defined CRMs, representing gap and pair-rule transcription factor binding sites. One predicted binding site for the gap transcription factor KRUPPEL in the IAB5 CRM was found to be altered in Superabdominal (Sab) mutations. In Sab mutant flies, the third abdominal segment is transformed into a copy of the fifth abdominal segment. A model for KRUPPEL-mediated repression at this binding site is presented. These findings challenge our current understanding of the relationship between sequence evolution at the molecular level and functional activity of a CRM. While the overall sequence conservation at Drosophila CRMs is not distinctive from neighboring genomic regions, functionally critical transcription factor binding sites within embryonic enhancer CRMs are highly conserved. These results have implications for understanding mechanisms of gene expression during embryonic development, enhancer function, and the molecular evolution of eukaryotic regulatory modules.