Cooperation between a hierarchical set of recruitment sites specifically targets the C. elegans dosage compensation complex to the X chromosomes.
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE87741 | GEO | 2017/05/09
SECONDARY ACCESSION(S): PRJNA347329
REPOSITORIES: GEO
Similar Datasets
Project description:In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the C. elegans X chromosome for repression by the DCC. The DCC binds to discrete, dispersed sites on X of two types. rex sites recruit the DCC in an autonomous, DNA sequence-dependent manner using a 12 bp consensus motif that is enriched on X. This motif is critical for DCC binding, is clustered in rex sites, and confers much of X-chromosome specificity. Motif variants enriched on X by 3.8-fold or more are highly predictive (95%) for rex sites. In contrast, dox sites lack the X-enriched variants and cannot bind the DCC when detached from X. dox sites are more prevalent than rex sites and, unlike rex sites, reside preferentially in promoters of some expressed genes. These findings fulfill predictions for a targeting model in which the DCC binds to recruitment sites on X and disperses to discrete sites lacking autonomous recruitment ability. To relate DCC binding to function, we identified dosage-compensated and non-compensated genes on X. Unexpectedly, many genes of both types have bound DCC, but many do not, suggesting the DCC acts over long distances to repress X gene expression. Remarkably, the DCC binds to autosomes, but at far fewer sites and rarely at consensus motifs. DCC disruption causes opposite effects on expression of X and autosomal genes. The DCC thus acts at a distance to impact expression throughout the genome. Experiment Overall Design: For microarray analysis, the nematode strains and number of experiments was as follows: TY2222, her-1(hv1y101); xol-1(y9) sdc-2(y74) unc-9(e101), XO embryos (8 biological replicas and 6 wild-type XX embryos controls ), dpy-27(y57) XX embryos (3 biological replicas and 3 wild-type XX embryos controls), and sdc-2(y93, RNAi) XX embryos (3 biological replicas and 3 wild-type XX embryos controls).
2009-03-07 | E-GEOD-14649 | biostudies-arrayexpress
Project description:Mechanisms establishing higher-order chromosome structures and their roles in gene regulation are elusive. We analyzed chromosome architecture during nematode X-chromosome dosage compensation, which represses transcription via a dosage-compensation condensin complex (DCC) that binds hermaphrodite Xs and establishes megabase-size topologically associating domains (TADs). We show that DCC binding at high-occupancy sites (rex sites) defines eight TAD boundary locations. Single rex deletions disrupted boundaries, and single insertions created new boundaries, demonstrating one rex site is necessary and sufficient for DCC-dependent boundary formation. Deleting eight rex sites (8rexΔ) recapitulated TAD structure of DCC mutants, permitting analysis when chromosome-wide domain architecture was disrupted but most DCC binding remained. 8rexΔ animals exhibited no changes in X expression and lacked dosage-compensation mutant phenotypes. Hence, TAD boundaries are neither the cause nor consequence of gene repression during dosage compensation. Abrogating TAD structure did, however, reduce thermotolerance, accelerate aging, and shorten lifespan, implicating chromosome architecture in regulating stress responses and aging.
2019-09-05 | GSE128566 | GEO
Project description:Mechanisms establishing higher-order chromosome structures and their roles in gene regulation are elusive. We analyzed chromosome architecture during nematode X-chromosome dosage compensation, which represses transcription via a dosage-compensation condensin complex (DCC) that binds hermaphrodite Xs and establishes megabase-size topologically associating domains (TADs). We show that DCC binding at high-occupancy sites (rex sites) defines eight TAD boundary locations. Single rex deletions disrupted boundaries, and single insertions created new boundaries, demonstrating one rex site is necessary and sufficient for DCC-dependent boundary formation. Deleting eight rex sites (8rexΔ) recapitulated TAD structure of DCC mutants, permitting analysis when chromosome-wide domain architecture was disrupted but most DCC binding remained. 8rexΔ animals exhibited no changes in X expression and lacked dosage-compensation mutant phenotypes. Hence, TAD boundaries are neither the cause nor consequence of gene repression during dosage compensation. Abrogating TAD structure did, however, reduce thermotolerance, accelerate aging, and shorten lifespan, implicating chromosome architecture in regulating stress responses and aging.
2019-09-05 | GSE128564 | GEO
Project description:Mechanisms establishing higher-order chromosome structures and their roles in gene regulation are elusive. We analyzed chromosome architecture during nematode X-chromosome dosage compensation, which represses transcription via a dosage-compensation condensin complex (DCC) that binds hermaphrodite Xs and establishes megabase-size topologically associating domains (TADs). We show that DCC binding at high-occupancy sites (rex sites) defines eight TAD boundary locations. Single rex deletions disrupted boundaries, and single insertions created new boundaries, demonstrating one rex site is necessary and sufficient for DCC-dependent boundary formation. Deleting eight rex sites (8rexΔ) recapitulated TAD structure of DCC mutants, permitting analysis when chromosome-wide domain architecture was disrupted but most DCC binding remained. 8rexΔ animals exhibited no changes in X expression and lacked dosage-compensation mutant phenotypes. Hence, TAD boundaries are neither the cause nor consequence of gene repression during dosage compensation. Abrogating TAD structure did, however, reduce thermotolerance, accelerate aging, and shorten lifespan, implicating chromosome architecture in regulating stress responses and aging.
2019-09-05 | GSE128559 | GEO
Project description:The three-dimensional (3D) organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure or how structure influences gene expression. Here we exploit the X-chromosome-wide process of dosage compensation to dissect these mechanisms. The dosage compensation complex (DCC) of C. elegans, a condensin complex, binds to both X chromosomes of hermaphrodites via sequence-specific recruitment sites (rex sites) to reduce chromosome-wide gene expression by half. Using genome-wide chromosome conformation capture and single-cell FISH to compare chromosome structure in wild-type and DCC-defective embryos (DC mutants), we show that the DCC remodels X chromosomes of hermaphrodites into a spatial conformation distinct from autosomes. The dosage-compensated X chromosomes are composed of Topologically Associating Domains (TADs) that have sharper boundaries and more regular spacing than TADs on autosomes. Most TAD boundaries on X coincide with the highest-affinity rex sites, and these boundaries are lost or diminished in DC mutants, thereby restoring the topology of X to a native conformation resembling that of autosomes. Although most rex sites engage in multiple strong DCC-dependent long-range interactions, the strongest interactions occur between rex sites at the DCC-dependent TAD boundaries. We propose the DCC actively shapes the topology of the entire X chromosome by forming new TAD boundaries and reinforcing pre-existing weak TAD boundaries through interactions between its highest affinity sites. Such changes in higher-order X-chromosome structure then influence gene expression over long distances.
2015-06-03 | GSE59715 | GEO
Project description:The three-dimensional (3D) organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure or how structure influences gene expression. Here we exploit the X-chromosome-wide process of dosage compensation to dissect these mechanisms. The dosage compensation complex (DCC) of C. elegans, a condensin complex, binds to both X chromosomes of hermaphrodites via sequence-specific recruitment sites (rex sites) to reduce chromosome-wide gene expression by half. Using genome-wide chromosome conformation capture and single-cell FISH to compare chromosome structure in wild-type and DCC-defective embryos (DC mutants), we show that the DCC remodels X chromosomes of hermaphrodites into a spatial conformation distinct from autosomes. The dosage-compensated X chromosomes are composed of Topologically Associating Domains (TADs) that have sharper boundaries and more regular spacing than TADs on autosomes. Most TAD boundaries on X coincide with the highest-affinity rex sites, and these boundaries are lost or diminished in DC mutants, thereby restoring the topology of X to a native conformation resembling that of autosomes. Although most rex sites engage in multiple strong DCC-dependent long-range interactions, the strongest interactions occur between rex sites at the DCC-dependent TAD boundaries. We propose the DCC actively shapes the topology of the entire X chromosome by forming new TAD boundaries and reinforcing pre-existing weak TAD boundaries through interactions between its highest affinity sites. Such changes in higher-order X-chromosome structure then influence gene expression over long distances.
2015-06-03 | GSE59597 | GEO
Project description:The three-dimensional (3D) organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure or how structure influences gene expression. Here we exploit the X-chromosome-wide process of dosage compensation to dissect these mechanisms. The dosage compensation complex (DCC) of C. elegans, a condensin complex, binds to both X chromosomes of hermaphrodites via sequence-specific recruitment sites (rex sites) to reduce chromosome-wide gene expression by half. Using genome-wide chromosome conformation capture and single-cell FISH to compare chromosome structure in wild-type and DCC-defective embryos (DC mutants), we show that the DCC remodels X chromosomes of hermaphrodites into a spatial conformation distinct from autosomes. The dosage-compensated X chromosomes are composed of Topologically Associating Domains (TADs) that have sharper boundaries and more regular spacing than TADs on autosomes. Most TAD boundaries on X coincide with the highest-affinity rex sites, and these boundaries are lost or diminished in DC mutants, thereby restoring the topology of X to a native conformation resembling that of autosomes. Although most rex sites engage in multiple strong DCC-dependent long-range interactions, the strongest interactions occur between rex sites at the DCC-dependent TAD boundaries. We propose the DCC actively shapes the topology of the entire X chromosome by forming new TAD boundaries and reinforcing pre-existing weak TAD boundaries through interactions between its highest affinity sites. Such changes in higher-order X-chromosome structure then influence gene expression over long distances.
2015-06-03 | GSE63717 | GEO
Project description:In D. melanogaster males, X chromosome monosomy is compensated by chromosome-wide transcription activation. We found that complete dosage compensation during embryogenesis takes surprisingly long. Although the activating Dosage Compensation Complex (DCC) associates with the chromosome and acetylates histone H4 early, many genes are not compensated. Acetylation levels on gene bodies continue to increase for several hours after gastrulation in parallel with progressive compensation. Constitutive genes are compensated earlier than developmental genes. Remarkably, later compensation correlates with longer distances to DCC binding sites. This time-space relationship suggests that DCC action on target genes requires maturation of the active chromosome compartment.
2019-06-28 | GSE127176 | GEO
Project description:In D. melanogaster males, X chromosome monosomy is compensated by chromosome-wide transcription activation. We found that complete dosage compensation during embryogenesis takes surprisingly long. Although the activating Dosage Compensation Complex (DCC) associates with the chromosome and acetylates histone H4 early, many genes are not compensated. Acetylation levels on gene bodies continue to increase for several hours after gastrulation in parallel with progressive compensation. Constitutive genes are compensated earlier than developmental genes. Remarkably, later compensation correlates with longer distances to DCC binding sites. This time-space relationship suggests that DCC action on target genes requires maturation of the active chromosome compartment.
2019-06-28 | GSE127175 | GEO
Project description:In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the C. elegans X chromosome for repression by the DCC. The DCC binds to discrete, dispersed sites on X of two types. rex sites recruit the DCC in an autonomous, DNA sequence-dependent manner using a 12 bp consensus motif that is enriched on X. This motif is critical for DCC binding, is clustered in rex sites, and confers much of X-chromosome specificity. Motif variants enriched on X by 3.8-fold or more are highly predictive (95%) for rex sites. In contrast, dox sites lack the X-enriched variants and cannot bind the DCC when detached from X. dox sites are more prevalent than rex sites and, unlike rex sites, reside preferentially in promoters of some expressed genes. These findings fulfill predictions for a targeting model in which the DCC binds to recruitment sites on X and disperses to discrete sites lacking autonomous recruitment ability. To relate DCC binding to function, we identified dosage-compensated and non-compensated genes on X. Unexpectedly, many genes of both types have bound DCC, but many do not, suggesting the DCC acts over long distances to repress X gene expression. Remarkably, the DCC binds to autosomes, but at far fewer sites and rarely at consensus motifs. DCC disruption causes opposite effects on expression of X and autosomal genes. The DCC thus acts at a distance to impact expression throughout the genome. Keywords: dosage compensation, condensin, X chromosome, gene expression, epigenetics, C. elegans ChIP-chip with DPY-27
2010-05-22 | E-GEOD-14651 | biostudies-arrayexpress