Unlabelled: Mechanisms of X chromosome dosage compensation have been studied extensively in a few model species representing clades of shared sex chromosome ancestry. However, the diversity within each clade as a function of sex chromosome evolution is largely unknown. Here, we anchor ourselves to the nematode , for which a well-studied mechanism of dosage compensation occurs through a specialized structural maintenance of chromosomes (SMC) complex, and explore the diversity of dosage compensation in the surrounding phylogeny of nematodes.
View Article and Find Full Text PDFRegulation of transcription during embryogenesis is key to development and differentiation. To study transcript expression throughout embryogenesis at single-molecule resolution, we developed a high-throughput single-molecule fluorescence in situ hybridization (smFISH) method that relies on computational methods to developmentally stage embryos and quantify individual mRNA molecules in single embryos. We applied our system to , a zygotically transcribed gene essential for hermaphrodite development and dosage compensation.
View Article and Find Full Text PDFIn mammals, cohesin and CTCF organize the 3D genome into topologically associated domains (TADs) to regulate communication between -regulatory elements. Many organisms, including , , and contain cohesin but lack CTCF. Here, we used to investigate the function of cohesin in 3D genome organization in the absence of CTCF.
View Article and Find Full Text PDFCondensins are molecular motors that compact DNA via linear translocation. In , the X-chromosome harbors a specialized condensin that participates in dosage compensation (DC). Condensin DC is recruited to and spreads from a small number of ecruitment lements on the -chromosome () and is required for the formation of topologically associating domains (TADs).
View Article and Find Full Text PDFCondensins are evolutionarily conserved molecular motors that translocate along DNA and form loops. To address how DNA topology affects condensin translocation, we applied auxin-inducible degradation of topoisomerases I and II and analyzed the binding and function of an interphase condensin that mediates X chromosome dosage compensation in C. elegans.
View Article and Find Full Text PDFIsolation of copy number variations and chromosomal duplications at high frequency in the laboratory suggested that Caenorhabditis elegans tolerates increased gene dosage. Here, we addressed if a general dosage compensation mechanism acts at the level of mRNA expression in C. elegans.
View Article and Find Full Text PDFCondensin is a multi-subunit structural maintenance of chromosomes (SMC) complex that binds to and compacts chromosomes. Here, we addressed the regulation of condensin binding dynamics using Caenorhabditis elegans condensin DC, which represses X chromosomes in hermaphrodites for dosage compensation. We established fluorescence recovery after photobleaching (FRAP) using the SMC4 homolog DPY-27 and showed that a well-characterized ATPase mutation abolishes DPY-27 binding to X chromosomes.
View Article and Find Full Text PDFThe auxin-inducible degradation system in C. elegans allows for spatial and temporal control of protein degradation via heterologous expression of a single Arabidopsis thaliana F-box protein, transport inhibitor response 1 (AtTIR1). In this system, exogenous auxin (Indole-3-acetic acid; IAA) enhances the ability of AtTIR1 to function as a substrate recognition component that adapts engineered degron-tagged proteins to the endogenous C.
View Article and Find Full Text PDFBackground: The transcription of developmental regulatory genes is often controlled by multiple cis-regulatory elements. The identification and functional characterization of distal regulatory elements remains challenging, even in tractable model organisms like sea urchins.
Results: We evaluate the use of chromatin accessibility, transcription and RNA Polymerase II for their ability to predict enhancer activity of genomic regions in sea urchin embryos.
Animals evolved in environments with variable nutrient availability and one form of adaptation is the delay of reproduction in food shortage conditions. Belew et al. (2021.
View Article and Find Full Text PDFAlthough precise tuning of gene expression levels is critical for most developmental pathways, the mechanisms by which the transcriptional output of dosage-sensitive molecules is established or modulated by the environment remain poorly understood. Here, we provide a mechanistic framework for how the conserved transcription factor BLMP-1/Blimp1 operates as a pioneer factor to decompact chromatin near its target loci during embryogenesis (hours prior to major transcriptional activation) and, by doing so, regulates both the duration and amplitude of subsequent target gene transcription during post-embryonic development. This priming mechanism is genetically separable from the mechanisms that establish the timing of transcriptional induction and functions to canalize aspects of cell-fate specification, animal size regulation, and molting.
View Article and Find Full Text PDFCondensins are evolutionarily conserved protein complexes that are required for chromosome segregation during cell division and genome organization during interphase. In , a specialized condensin, which forms the core of the dosage compensation complex (DCC), binds to and represses chromosome transcription. Here, we analyzed DCC localization and the effect of DCC depletion on histone modifications, transcription factor binding, and gene expression using chromatin immunoprecipitation sequencing and mRNA sequencing.
View Article and Find Full Text PDFCondensin is a multi-subunit protein complex that belongs to the family of structural maintenance of chromosomes (SMC) complexes. Condensins regulate chromosome structure in a wide range of processes including chromosome segregation, gene regulation, DNA repair and recombination. Recent research defined the structural features and molecular activities of condensins, but it is unclear how these activities are connected to the multitude of phenotypes and functions attributed to condensins.
View Article and Find Full Text PDFRecent work demonstrating the role of chromosome organization in transcriptional regulation has sparked substantial interest in the molecular mechanisms that control chromosome structure. Condensin, an evolutionarily conserved multisubunit protein complex, is essential for chromosome condensation during cell division and functions in regulating gene expression during interphase. In Caenorhabditis elegans, a specialized condensin forms the core of the dosage compensation complex (DCC), which specifically binds to and represses transcription from the hermaphrodite X chromosomes.
View Article and Find Full Text PDFIn many organisms, it remains unclear how X chromosomes are specified for dosage compensation, since DNA sequence motifs shown to be important for dosage compensation complex (DCC) recruitment are themselves not X-specific. Here, we addressed this problem in . We found that the DCC recruiter, SDC-2, is required to maintain open chromatin at a small number of primary DCC recruitment sites, whose sequence and genomic context are X-specific.
View Article and Find Full Text PDFDosage compensation mechanisms equalize the level of X chromosome expression between sexes. Yet the X chromosome is often enriched for genes exhibiting sex-biased, i.e.
View Article and Find Full Text PDFIn Caenorhabditis elegans, the dosage compensation complex (DCC) specifically binds to and represses transcription from both X chromosomes in hermaphrodites. The DCC is composed of an X-specific condensin complex that interacts with several proteins. During embryogenesis, DCC starts localizing to the X chromosomes around the 40-cell stage, and is followed by X-enrichment of H4K20me1 between 100-cell to comma stage.
View Article and Find Full Text PDFIn many animals, males have one X and females have two X chromosomes. The difference in X chromosome dosage between the two sexes is compensated by mechanisms that regulate X chromosome transcription. Recent advances in genomic techniques have provided new insights into the molecular mechanisms of X chromosome dosage compensation.
View Article and Find Full Text PDFGenome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization.
View Article and Find Full Text PDFStudies of X chromosome evolution in various organisms have indicated that sex-biased genes are nonrandomly distributed between the X and autosomes. Here, to extend these studies to nematodes, we annotated and analyzed X chromosome gene content in four Caenorhabditis species and in Pristionchus pacificus. Our gene expression analyses comparing young adult male and female mRNA-seq data indicate that, in general, nematode X chromosomes are enriched for genes with high female-biased expression and depleted of genes with high male-biased expression.
View Article and Find Full Text PDFIn recent years, Caenorhabditis elegans has emerged as a new model to investigate the relationships between nuclear architecture, cellular differentiation, and organismal development. On one hand, C. elegans with its fixed lineage and transparent body is a great model organism to observe gene functions in vivo in specific cell types using microscopy.
View Article and Find Full Text PDFCold Spring Harb Perspect Biol
March 2014
Dosage compensation, which regulates the expression of genes residing on the sex chromosomes, has provided valuable insights into chromatin-based mechanisms of gene regulation. The nematode Caenorhabditis elegans has adopted various strategies to down-regulate and even nearly silence the X chromosomes. This article discusses the different chromatin-based strategies used in somatic tissues and in the germline to modulate gene expression from the C.
View Article and Find Full Text PDFBackground: Condensins are multi-subunit protein complexes that are essential for chromosome condensation during mitosis and meiosis, and play key roles in transcription regulation during interphase. Metazoans contain two condensins, I and II, which perform different functions and localize to different chromosomal regions. Caenorhabditis elegans contains a third condensin, I(DC), that is targeted to and represses transcription of the X chromosome for dosage compensation.
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