Chromosomal High Affinity Binding Sites for the Drosophila Dosage Compensation Complex.
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ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE12292 | GEO | 2008/12/14
SECONDARY ACCESSION(S): PRJNA113583
REPOSITORIES: GEO
Similar Datasets
Project description:We identified 131 high affinity sites of the Drosophila DCC combining residual ChIP-chip profiles after differential crosslinking and RNAi-mediated knockdown of spreading factors Keywords: ChIP-chip MSL1 and MSL2 ChIP under various conditions including differential crosslinking and RNAi against MOF, MLE and MSL3. 2-4 replicates per experiment. dye-swaps as indicated in sample description.
2008-12-13 | E-GEOD-12292 | biostudies-arrayexpress
Project description:Among organisms with chromosome-based mechanisms of sex determination, failure to equalize expression of X-linked genes between the sexes is typically lethal. In C. elegans, XX hermaphrodites halve transcription from each X chromosome to match the output of XO males1. Here, we mapped the binding location of the condensin homolog DPY-27 and the zinc finger protein SDC-3, two components of the C. elegans dosage compensation complex (DCC)2,3. Strong foci of DCC binding were observed on X, around which broader regions of localization were centered. Binding foci, but not adjacent regions of localization, were distinguished by clusters of a stereotypic 10-bp DNA sequence, suggesting a recruitment-and-spreading mechanism for X recognition. In contrast to the Drosophila DCC, the C. elegans DCC was bound preferentially upstream of genes, suggesting modulation of transcriptional initiation and transcription-coupled spreading. A mechanism for tuning DCC activity at specific loci was indicated by stronger DCC binding upstream of genes with high transcriptional activity. These data provide a basis for understanding how proteins involved in higher-order chromosome dynamics can regulate transcription at individual loci. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Keywords: ChIP-chip dosage compensation complex
2007-02-11 | GSE6739 | GEO
Project description:In 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. Here, we analyzed dosage compensation of the X chromosome between sexes, and the roles of dpy-27 (condensin subunit), dpy-21 (non-condensin DCC member), set-1 (H4K20 monomethylase) and set-4 (H4K20 di-/tri-methylase) in X chromosome repression using mRNA-seq and ChIP-seq analyses across several developmental time points. We found that the DCC starts repressing the X chromosomes by the 40-cell stage, but X-linked transcript levels remain significantly higher in hermaphrodites compared to males through the comma stage of embryogenesis. Dpy-27 and dpy-21 are required for X chromosome repression throughout development, but particularly in early embryos dpy-27 and dpy-21 mutations produced distinct expression changes, suggesting a DCC independent role for dpy-21. We previously hypothesized that the DCC increases H4K20me1 by reducing set-4 activity on the X chromosomes. Accordingly, in the set-4 mutant, H4K20me1 increased more from the autosomes compared to the X, equalizing H4K20me1 level between X and autosomes. H4K20me1 increase on the autosomes led to a slight repression, resulting in a relative effect of X derepression. H4K20me1 depletion in the set-1 mutant showed greater X derepression compared to equalization of H4K20me1 levels between X and autosomes in the set-4 mutant, indicating that H4K20me1 level is important, but X to autosomal balance of H4K20me1 contributes only slightly to X-repression. Thus H4K20me1 by itself is not a downstream effector of the DCC. In summary, X chromosome dosage compensation starts in early embryos as the DCC localizes to the X, and is strengthened in later embryogenesis by H4K20me1.
2015-11-09 | GSE67650 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE14649: DCC binding and function (Expression Analysis) GSE14650: DCC binding and function (ChIP-chip: SDC-3, MIX-1, DPY-27, Mock) GSE14651: DCC binding and function (ChIP-chip: DPY-27) GSE14652: DCC binding and function (ChIP-chip: SDC-2) GSE14653: DCC binding and function (ChIP-chip: SDC-3, DPY-27, Mock) Refer to individual Series
2010-05-22 | E-GEOD-14640 | biostudies-arrayexpress
Project description:In 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. Here, we analyzed dosage compensation of the X chromosome between sexes, and the roles of dpy-27 (condensin subunit), dpy-21 (non-condensin DCC member), set-1 (H4K20 monomethylase) and set-4 (H4K20 di-/tri-methylase) in X chromosome repression using mRNA-seq and ChIP-seq analyses across several developmental time points. We found that the DCC starts repressing the X chromosomes by the 40-cell stage, but X-linked transcript levels remain significantly higher in hermaphrodites compared to males through the comma stage of embryogenesis. Dpy-27 and dpy-21 are required for X chromosome repression throughout development, but particularly in early embryos dpy-27 and dpy-21 mutations produced distinct expression changes, suggesting a DCC independent role for dpy-21. We previously hypothesized that the DCC increases H4K20me1 by reducing set-4 activity on the X chromosomes. Accordingly, in the set-4 mutant, H4K20me1 increased more from the autosomes compared to the X, equalizing H4K20me1 level between X and autosomes. H4K20me1 increase on the autosomes led to a slight repression, resulting in a relative effect of X derepression. H4K20me1 depletion in the set-1 mutant showed greater X derepression compared to equalization of H4K20me1 levels between X and autosomes in the set-4 mutant, indicating that H4K20me1 level is important, but X to autosomal balance of H4K20me1 contributes only slightly to X-repression. Thus H4K20me1 by itself is not a downstream effector of the DCC. In summary, X chromosome dosage compensation starts in early embryos as the DCC localizes to the X, and is strengthened in later embryogenesis by H4K20me1. RNA-Seq profiles of C. elegans wild type hermaphrodite, mixed sex, at 5 time points and dpy-27, set-4, dpy-21, set-1 and RNAi at 2-3 time points with 3-4 replicates each. RNA-Seq profiles of C. elegans. Strains are N2 (wild type), BS553 fog-2(oz40) V, CB428 dpy-21(e428) V, MK4 dpy-27(y56) III, MT14911 set-4 (n4600) II, SS1075 set-1(tm1821)/hT2g[bli-4(e937) let-?(q782) qIs48] (I;III). Set-1 collections made as heterozygotes and dpy-27(y56) homozygotes. Spike in RNA-seq libraries have AF16 wild type C. briggsae L1s added at a 1:10 ratio. Timepoints are early embryos (synchronized collection, <40 cells), comma embryos (synchronized early embryos aged for 4 hours), mixed embryos (mixed stage embryos from unsynchronized population), L1 (synchronized L1 larvae), L3 (synchronized L3 larvae), and YA (synchronized young adults, collected before embryos present in hermaphrodite gonad). Biological replicates for each strain/stage listed separately. ChIP-seq profiles of C. elegans DCC subunit dpy-27, H4K20me1 histone modification and RNA pol II large subunit ama-1 in 3-6 replicates from mixed stage (unsynchronized) embryos and synchronized L3 larvae. Corresponding inputs are labelled with "Input_" plus ChIP name.
2015-11-09 | E-GEOD-67650 | biostudies-arrayexpress
Project description:The genetic mechanisms that allow specific targeting of large chromosomal domains by various gene regulatory complexes remain unclear. Here, we used the C. elegans dosage compensation system to study how binding of a condensin-like dosage compensation complex (DCC) is specifically targeted to the X chromosomes. Previous work established that the DCC is first recruited to a small number of recruitment sites before subsequently spreading in cis along the X chromosome. To understand X-specificity of DCC recruitment, we examined the genomic properties of the recruitment sites and analyzed DCC binding upon ectopic insertion and deletion of recruitment site sequence. We find that X-specificity of DCC recruitment is the combined result of hierarchical recognition of and long-distance cooperation between the recruitment sites.
2017-05-09 | GSE87741 | GEO
Project description:Dosage compensation in male Drosophila relies on the X chromosome-specific recruitment of a chromatin-modifying machinery, the dosage compensation complex (DCC). The principles that assure selective targeting of the DCC are unknown. According to a prevalent model, X chromosome targeting is initiated by recruitment of the DCC core components, MSL1 and MSL2, to a limited number of so-called "high-affinity sites" (HAS). Only very few such sites are known at the DNA sequence level, which has precluded the definition of DCC targeting principles. Combining RNA interference against DCC subunits, limited crosslinking, and chromatin immunoprecipitation coupled to probing high-resolution DNA microarrays, we identified a set of 131 HAS for MSL1 and MSL2 and confirmed their properties by various means. The HAS sites are distributed all over the X chromosome and are functionally important, since the extent of dosage compensation of a given gene and its proximity to a HAS are positively correlated. The sites are mainly located on non-coding parts of genes and predominantly map to regions that are devoid of nucleosomes. In contrast, the bulk of DCC binding is in coding regions and is marked by histone H3K36 methylation. Within the HAS, repetitive DNA sequences mainly based on GA and CA dinucleotides are enriched. Interestingly, DCC subcomplexes bind a small number of autosomal locations with similar features.
| S-EPMC2586088 | biostudies-literature
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:The male-specific dosage compensation complex (DCC), which consists of five proteins and two non-coding roX RNAs, is necessary for the transcriptional enhancement of X-linked genes to compensate for the sex chromosome monosomy in Drosophila XY males, compared with XX females. The MSL1 and MSL2 proteins form the heterotetrameric core of DCC and are critical for the specific recruitment of the DCC to the high-affinity “entry” sites (HAS) on the X chromosome. Here we demonstrated that the N-terminal region of MSL1 is critical for its stability and functions. Amino acid deletions and substitutions in the N-terminal region of MSL1 strongly affect both interaction with roX2 RNA and DCC binding to HAS on the X chromosome. In particular, substitution of the conserved N-terminal amino-acids 3-7 in MSL1GS has an affect on dosage compensation similar to inactivation of genes encoding roX RNAs. MSL1GS binds to promoters like MSL1WT but does not co-bind with MSL2 and MSL3 to X chromosomal HAS. However, over-expression of MSL2 partially restores the functional activity of MSL1GS in dosage compensation. Thus, the interaction of MSL1 with roX RNA is critical for the efficient assembly of DCCs on HAS of the male X chromosome.
2024-11-30 | GSE243396 | 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