Highly structured homolog pairing reflects functional organization of the Drosophila genome
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PROVIDER: PRJNA496497 | ENA |
REPOSITORIES: ENA
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Project description:Trans-homolog interactions encompass potent regulatory functions, which have been studied extensively in Drosophila, where homologs are paired in somatic cells and pairing-dependent gene regulation, or transvection, is well-documented. Nevertheless, the structure of pairing and whether its functional impact is genome-wide have eluded analysis. Accordingly, we generated a diploid cell line from divergent parents and applied haplotype-resolved Hi-C, discovering that homologs pair relatively precisely genome-wide in addition to establishing trans-homolog domains and compartments. We also elucidated the structure of pairing with unprecedented detail, documenting significant variation across the genome. In particular, we characterized two forms: tight pairing, consisting of contiguous small domains, and loose pairing, consisting of single larger domains. Strikingly, active genomic regions (A-type compartments, active chromatin, expressed genes) correlated with tight pairing, suggesting that pairing has a functional role genome-wide. Finally, using RNAi and haplotype-resolved Hi-C, we show that disruption of pairing-promoting factors results in global changes in pairing.
2018-10-16 | GSE121256 | GEO
Project description: Not available
| S-EPMC6776532 | biostudies-literature
Project description:Genome organization involves cis and trans chromosomal interactions, both implicated in gene regulation, development, and disease. Here, we focused on trans interactions in Drosophila, where homologous chromosomes are paired in somatic cells from embryogenesis through adulthood. We first addressed the long-standing question of whether pairing extends genome-wide and, to this end, developed a haplotype-resolved Hi-C approach that uses a new strategy to minimize homolog misassignment and thus robustly distinguish trans-homolog from cis contacts. This approach revealed striking genome-wide pairing in Drosophila embryos. Moreover, we discovered pairing to be surprisingly structured, with trans-homolog domains and interaction peaks, many coinciding with the positions of analogous cis features. We also found a significant correlation between pairing and the chromatin accessibility mediated by the pioneer factor Zelda. Our findings reveal a complex, highly structured organization underlying homolog pairing, first discovered more than a century ago.
2018-10-16 | GSE121255 | GEO
Project description:Two different models have been proposed to explain how the endpoints of chromatin looped domains (“TADs”) in eukaryotic chromosomes are determined. In the first a cohesin complex extrudes a loop until it encounters a boundary element roadblock, generating a stem-loop (and an unanchored loop). In this model, boundaries are functionally autonomous: they have an intrinsic ability to halt the movement of incoming cohesin complexes that is independent of the properties of neighboring boundaries. In the second, loops are generated by boundary:boundary pairing. In this model, boundaries are functionally non-autonomous, and their ability to form a loop depends upon how well they match with their neighbors. Moreover, unlike the loop-extrusion model, pairing interactions can generate both stem-loops and circle-loops. We have used a combination of Micro-C to analyze how TADs are organized and experimental manipulations of the even-skipped TAD boundary, homie, to test the predictions of the “loop-extrusion” and the “boundary-pairing” models. Our findings are incompatible with the loop-extrusion model and instead suggest that endpoints of TADs in flies are determined by a mechanism in which boundary elements physically pair with their neighbors, either head-to-head, or head-to-tail.
2024-02-25 | GSE222999 | GEO
Project description:During meiosis, chromosomes undergo extensive changes in structure and intranuclear positioning. How these chromosome organization changes occur and how they influence meiosis-specific chromosome events are not fully understood. Using Hi-C, we characterized chromosome architecture throughout mouse spermatogenesis at high temporal resolution. Our study revealed an intimate link between chromosome organization features and homolog pairing and alignment. We found that the meiotic chromosomes progressively reshape from TAD-like domains into linearly arranged loop arrays during prophase I. The transcriptionally active and inactive genomic regions exhibit distinct dynamics of loop growth, resulting in alternating domains consisting of shorter and longer chromosome loops. Such a domanial organization along meiotic chromosome axes is tightly correlated with the strength and precision of inter-homolog alignment. We further showed that a significant fraction of chromosomes near chromosome ends exhibit elevated inter-chromosomal association upon entering zygotene stage, while also exhibiting a higher degree of inter-homolog alignment. Using a mouse model defective in LINC complex component SUN1, we demonstrated that the prominent alignment of chromosome ends is dependent on the association of telomeres with the mechano-transducing LINC complex, but not the tethering of telomeres to the nuclear periphery. Taken together, our results suggest the 3D chromosome organization may provide a structural framework for the regulation of meiotic chromosome processes in higher eukaryotes.
2021-08-25 | GSE155638 | GEO
Project description:During meiosis, chromosomes undergo extensive changes in structure and intranuclear positioning. How these chromosome organization changes occur and how they influence meiosis-specific chromosome events are not fully understood. Using Hi-C, we characterized chromosome architecture throughout mouse spermatogenesis at high temporal resolution. Our study revealed an intimate link between chromosome organization features and homolog pairing and alignment. We found that the meiotic chromosomes progressively reshape from TAD-like domains into linearly arranged loop arrays during prophase I. The transcriptionally active and inactive genomic regions exhibit distinct dynamics of loop growth, resulting in alternating domains consisting of shorter and longer chromosome loops. Such a domanial organization along meiotic chromosome axes is tightly correlated with the strength and precision of inter-homolog alignment. We further showed that a significant fraction of chromosomes near chromosome ends exhibit elevated inter-chromosomal association upon entering zygotene stage, while also exhibiting a higher degree of inter-homolog alignment. Using a mouse model defective in LINC complex component SUN1, we demonstrated that the prominent alignment of chromosome ends is dependent on the association of telomeres with the mechano-transducing LINC complex, but not the tethering of telomeres to the nuclear periphery. Taken together, our results suggest the 3D chromosome organization may provide a structural framework for the regulation of meiotic chromosome processes in higher eukaryotes.
2021-08-25 | GSE155967 | GEO
Project description: Not available
| S-EPMC7756592 | biostudies-literature
Project description:The budding yeast Saccharomyces cerevisiae is a long-standing model for the three-dimensional organization of eukaryotic genomes1,2, and recent high-throughput chromatin conformation capture (Hi-C)2 methods have allowed systematic and unbiased measurement of this organization. Using polymer modeling, some groups have suggested that yeast genome conformation is simple and dominated by its Rabl-like orientation (anaphase-like polarization)3,4. Others have argued that yeast genome conformation is influenced by homolog pairing in diploids5–7 and environment-induced gene relocalization8–13, but the generality and extent of these phenomena remain unclear14. Here, we perform Hi-C on diverged Saccharomyces hybrid diploids to obtain the first global view of chromosome conformation in diploid budding yeasts. Previous studies of homolog pairing have attempted to control for the Rabl-like orientation14, but genomic analysis combined with polymer modeling reveals underappreciated contributions of the Rabl-like orientation to homolog proximity. After controlling for these features, we observe a residual signature of homolog proximity, particularly in saturated phase. From these same data, we also identify known and unexpected inducible gene repositioning. We observe that GAL1 shifts away from the centromere cluster upon galactose induction, consistent with reports of peripheral relocalization8,15. Surprisingly, under galactose induction and saturated phase, we observe a localized increase in homologous interactions between the HAS1 alleles, mediated by association with nuclear pore complexes. The discovery of this conformational change in such well-studied conditions suggests that our understanding of inducible genome reorganization remains incomplete. Together, these results reveal that the diploid yeast genome displays dynamic and complex 3D organization.
2016-12-05 | GSE88952 | GEO
Project description:Structured elements drive extensive circular RNA translation
| PRJNA740184 | ENA
Project description: Not available
| S-EPMC4344196 | biostudies-literature