Caenorhabditis elegans  Dosage Compensation: Insights into Condensin-Mediated Gene Regulation

Albritton, Sarah Elizabeth; Ercan, Sevinç

doi:10.1016/j.tig.2017.09.010

Cited by 36 publications

(40 citation statements)

References 100 publications

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“…Given that MLE specifically recognizes stem structures containing U-rich roX-box sequences (9)(10)(11), the sequence specificity to U-rich single stranded sequences must come from the helicase core of MLE as has been shown before (18). 1 H, 15 N HSQC NMR titration experiments with a slightly shorter version of SL7 roX-box region capped at one end with the apical loop of SL7 (SL7 14merLoop ) to prevent sliding of dsRBD1,2 on the RNA showed minimal line broadening. As both domains showed simultaneous binding to SL7 14merLoop RNA as confirmed by chemical shift perturbations in both domains upon SL7 14merLoop titration and filter binding experiments, we can conclude that both domains in the tandem construct bind to this RNA.…”

Section: Discussionmentioning

confidence: 93%

“…To avoid a lethal imbalance of X-linked gene expression levels, different mechanisms of dosage compensation have evolved (1)(2)(3). In Drosophila males, the male-specific-lethal (MSL) complex binds with remarkable X-chromosome specificity to PionX sites (4), spreads out along the X-chromosome and achieves two-fold hypertranscription (5).…”

Section: Introductionmentioning

confidence: 99%

“…(A)1 H,15 N-HSQC NMR spectrum of dsRBD1,2 (black), dsRBD1 (green) and dsRBD2 (blue) are shown. No major chemical shift differences between the three spectra could be observed suggesting that the two domains act as independent modules in solution.…”

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confidence: 99%

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Structure, dynamics and roX2-lncRNA binding of tandem double-stranded RNA binding domains dsRBD1,2 of Drosophila helicase Maleless

Jagtap¹,

Müller

Masiewicz³

et al. 2018

Preprint

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Maleless (MLE) is an evolutionary conserved member of the DExH family of helicases in Drosophila.Besides its function in RNA editing and presumably siRNA processing, MLE is best known for its role in remodelling non-coding roX RNA in the context of X chromosome dosage compensation in male flies.MLE and its human orthologue, DHX9 contain two tandem double-stranded RNA binding domains (dsRBDs) located at the N-terminal region. The two dsRBDs are essential for localization of MLE at the X-territory and it is presumed that this involves binding roX secondary structures. However, for dsRBD1 roX RNA binding has so far not been described. Here, we determined the solution NMR structure of dsRBD1 and dsRBD2 of MLE in tandem and investigated its role in double-stranded RNA (dsRNA) binding. Our NMR data show that both dsRBDs act as independent structural modules in solution and are canonical, non-sequence-specific dsRBDs featuring non-canonical KKxAK RNA binding motifs.NMR titrations combined with filter binding experiments document the contribution of dsRBD1 to dsRNA binding in vitro. Curiously, dsRBD1 mutants in which dsRNA binding in vitro is strongly compromised do not affect roX2 RNA binding and MLE localization in cells. These data suggest alternative functions for dsRBD1 in vivo.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Structure, dynamics and roX2-lncRNA binding of tandem double-stranded RNA binding domains dsRBD1,2 of Drosophila helicase Maleless

Jagtap¹,

Müller

Masiewicz³

et al. 2018

Preprint

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“…Metazoans contain two types of condensin complexes (I and II) that share a heterodimer of two 'structural maintenance of chromosomes' (SMC) proteins, SMC2 and SMC4, and are distinguished by three unique CAP (chromosome-associated polypeptide) proteins named CAPG, CAPD and CAPH (47). Uniquely, C. elegans has an additional complex, condensin-IDC, which contributes exclusively to dosage compensation in somatic cells (48). KLE-2, HCP-6 and CAPG-2 are condensin-II specific subunits, CAPG-1, DPY-26 and DPY-28 are common to the two condensin-I complexes, whereas DPY-27 is specific to condensin-IDC ( Figure 2A) (46).…”

Section: Loss Of Set-2 Enhances Chromosome Organization Defects Resulmentioning

confidence: 99%

Cooperation between Caenorhabditis elegans COMPASS and condensin in germline chromatin organization

Herbette

Robert

Bailly

et al. 2020

Preprint

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Background Histone-modifying activities play important roles in gene expression and influence higher-order genome organization. SET1/COMPASS (Complex Proteins Associated with Set1) deposits h istone H3 lysine 4 (H3K4) methylation at promoter regions and is associated with context-dependent effects on gene expression. Whether it also contributes to higher-order chromosome organization has not been explored. Results Using a quantitative FRET (Förster resonance energy transfer)-based fluorescence lifetime imaging microscopy (FLIM) approach to assay nanometer scale chromatin compaction in live animals, we reveal a novel role for SET1/COMPASS in structuring meiotic chromosomes in the C. elegans germline . Inactivation of SET-2, the C. elegans homologue of SET1, strongly enhanced chromosome organization defects and loss of fertility resulting from depletion of condensin-II, and aggravated defects in chromosome morphology resulting from inactivation of topoisomerase II, another major structural component of chromosomes. Loss of CFP-1, the chromatin targeting subunit of COMPASS, similarly affected germline chromatin compaction measured by FLIM-FRET and enhanced condensin-II knock-down phenotypes. Conclusions The data presented here are consistent with a role of SET1/ COMPASS in shaping meiotic chromosomes in the C. elegans germline. This new insight has important implications for how c hromatin-modifying complexes and histone modifications may cooperate with non histone-proteins to achieve proper chromosome organization, not only in meiosis, but also in mitosis.

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“…Here we addressed the link between condensin and transcription by using a clear paradigm for the gene-regulatory function of condensins, the C. elegans dosage compensation complex (DCC) [6].…”

Section: Introductionmentioning

confidence: 99%

Binding of an X-specific condensin correlates with a reduction in active histone modifications at gene regulatory elements

Street

Morao

Winterkorn

et al. 2019

Preprint

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Condensins are evolutionarily conserved protein complexes that are required for chromosome segregation during cell division and genome organization during interphase. In C. elegans, a specialized condensin, which forms the core of the dosage compensation complex (DCC) binds to and represses X chromosome transcription. Here, we analyzed DCC localization and effect of DCC depletion and binding on histone modifications, transcription factor binding, and gene expression using ChIP-seq and mRNA-seq. Across the X, DCC binding coincides with gene regulatory sites at active chromatin and not heterochromatin. DCC is required for reducing the levels of active histone modifications, including H3K4me3 and H3K27ac, but not repressive modification H3K9me3 on the X. In X-to-autosome fusion chromosomes, DCC spreading into the autosomal sequences locally reduces the level of H3K4me3 and gene expression. Together, our results suggest that DCC fine-tunes X chromosomal transcription by binding to and modulating the activity of gene regulatory elements through reducing activating histone modifications.

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Caenorhabditis elegans Dosage Compensation: Insights into Condensin-Mediated Gene Regulation

Cited by 36 publications

References 100 publications

Structure, dynamics and roX2-lncRNA binding of tandem double-stranded RNA binding domains dsRBD1,2 of Drosophila helicase Maleless

Structure, dynamics and roX2-lncRNA binding of tandem double-stranded RNA binding domains dsRBD1,2 of Drosophila helicase Maleless

Cooperation between Caenorhabditis elegans COMPASS and condensin in germline chromatin organization

Binding of an X-specific condensin correlates with a reduction in active histone modifications at gene regulatory elements

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