Browsing by Author "Maxwell, Colin S"

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    Intergenerational Effects of Dietary Restriction and Insulin/IGF Signaling on Starvation Resistance and Reproductive Development
    (2018-10-02) Jordan, James M; Hibshman, Jonathan D; Kaplan, Rebecca EW; Webster, Amy K; Leinroth, Abigail; Maxwell, Colin S; Bowman, Elizabeth Anne; Hubbard, E Jane Albert; Baugh, L Ryan
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    Nutritional control of mRNA isoform expression during developmental arrest and recovery in C. elegans.
    (Genome Res, 2012-10) Maxwell, Colin S; Antoshechkin, Igor; Kurhanewicz, Nicole; Belsky, Jason A; Baugh, L Ryan
    Nutrient availability profoundly influences gene expression. Many animal genes encode multiple transcript isoforms, yet the effect of nutrient availability on transcript isoform expression has not been studied in genome-wide fashion. When Caenorhabditis elegans larvae hatch without food, they arrest development in the first larval stage (L1 arrest). Starved larvae can survive L1 arrest for weeks, but growth and post-embryonic development are rapidly initiated in response to feeding. We used RNA-seq to characterize the transcriptome during L1 arrest and over time after feeding. Twenty-seven percent of detectable protein-coding genes were differentially expressed during recovery from L1 arrest, with the majority of changes initiating within the first hour, demonstrating widespread, acute effects of nutrient availability on gene expression. We used two independent approaches to track expression of individual exons and mRNA isoforms, and we connected changes in expression to functional consequences by mining a variety of databases. These two approaches identified an overlapping set of genes with alternative isoform expression, and they converged on common functional patterns. Genes affecting mRNA splicing and translation are regulated by alternative isoform expression, revealing post-transcriptional consequences of nutrient availability on gene regulation. We also found that phosphorylation sites are often alternatively expressed, revealing a common mode by which alternative isoform expression modifies protein function and signal transduction. Our results detail rich changes in C. elegans gene expression as larvae initiate growth and post-embryonic development, and they provide an excellent resource for ongoing investigation of transcriptional regulation and developmental physiology.
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    Pol II docking and pausing at growth and stress genes in C. elegans.
    (Cell Rep, 2014-02-13) Maxwell, Colin S; Kruesi, William S; Core, Leighton J; Kurhanewicz, Nicole; Waters, Colin T; Lewarch, Caitlin L; Antoshechkin, Igor; Lis, John T; Meyer, Barbara J; Baugh, L Ryan
    Fluctuations in nutrient availability profoundly impact gene expression. Previous work revealed postrecruitment regulation of RNA polymerase II (Pol II) during starvation and recovery in Caenorhabditis elegans, suggesting that promoter-proximal pausing promotes rapid response to feeding. To test this hypothesis, we measured Pol II elongation genome wide by two complementary approaches and analyzed elongation in conjunction with Pol II binding and expression. We confirmed bona fide pausing during starvation and also discovered Pol II docking. Pausing occurs at active stress-response genes that become downregulated in response to feeding. In contrast, "docked" Pol II accumulates without initiating upstream of inactive growth genes that become rapidly upregulated upon feeding. Beyond differences in function and expression, these two sets of genes have different core promoter motifs, suggesting alternative transcriptional machinery. Our work suggests that growth and stress genes are both regulated postrecruitment during starvation but at initiation and elongation, respectively, coordinating gene expression with nutrient availability.