Highly structured homolog pairing reflects functional organization of the Drosophila genome

Abed, Jumana AlHaj; Erceg, Jelena; Goloborodko, Anton; Nguyen, Son C.; McCole, Ruth B.; Saylor, Wren; Fudenberg, Geoffrey; Lajoie, Bryan R.; Dekker, Job; Mirny, Leonid A.; Wu, Chao-ting

doi:10.1038/s41467-019-12208-3

Cited by 58 publications

(81 citation statements)

References 78 publications

(114 reference statements)

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“…Since PSS is thought to be dependent upon homolog pairing, the different properties of the five insertion sites could be due to differences in the strength of local homolog pairing. To investigate this possibility, we took advantage of a recent genome-wide study that measured interaction frequencies between homologs at the embryo stage [ 64 ]. However, analysis of the available Hi-C data did not show any significant correlations (Additional file 2 ).…”

Section: Resultsmentioning

confidence: 99%

Boundaries potentiate polycomb response element-mediated silencing

et al. 2021

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Background Epigenetic memory plays a critical role in the establishment and maintenance of cell identities in multicellular organisms. Polycomb and trithorax group (PcG and TrxG) proteins are responsible for epigenetic memory, and in flies, they are recruited to specialized DNA regulatory elements termed polycomb response elements (PREs). Previous transgene studies have shown that PREs can silence reporter genes outside of their normal context, often by pairing sensitive (PSS) mechanism; however, their silencing activity is non-autonomous and depends upon the surrounding chromatin context. It is not known why PRE activity depends on the local environment or what outside factors can induce silencing. Results Using an attP system in Drosophila, we find that the so-called neutral chromatin environments vary substantially in their ability to support the silencing activity of the well-characterized bxdPRE. In refractory chromosomal contexts, factors required for PcG-silencing are unable to gain access to the PRE. Silencing activity can be rescued by linking the bxdPRE to a boundary element (insulator). When placed next to the PRE, the boundaries induce an alteration in chromatin structure enabling factors critical for PcG silencing to gain access to the bxdPRE. When placed at a distance from the bxdPRE, boundaries induce PSS by bringing the bxdPREs on each homolog in close proximity. Conclusion This proof-of-concept study demonstrates that the repressing activity of PREs can be induced or enhanced by nearby boundary elements. Graphical abstract

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Section: Resultsmentioning

confidence: 99%

Boundaries potentiate polycomb response element-mediated silencing

et al. 2021

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“…As the male chrX is the only chromosome without a paired homologue, we asked if this male chrX peculiarity may affect the observed differences in the interaction decay profile. To this concern, recent independent studies presenting haplotype-resolved Hi-C data show that the ratio of inter-homologous interactions vs cis -interactions increases at mid-/long-range distances 38,39 . Thus, the lack of a homologous chromosome may result in less mid-/long-range contacts being detected, i.e.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, to definitely disentangle the contribution of homologous chromosomes pairing to the interaction decay profile, we applied polymer folding simulation techniques. Abed et al 39 reported that the level of pairing is correlated to the local chromatin state, which in turn is known to affect the pattern of Hi-C contacts 16,40–42 . Therefore, we applied a polymer folding simulation model accounting for chromatin states annotations in the D. melanogaster genome as well as distribution of homologous tight pairing parameters in line with Abed et al 39 estimations (see Methods).…”

Section: Resultsmentioning

confidence: 99%

Global chromatin conformation differences in the Drosophila dosage compensated chromosome X

et al. 2019

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In Drosophila melanogaster the single male chromosome X undergoes an average twofold transcriptional upregulation for balancing the transcriptional output between sexes. Previous literature hypothesised that a global change in chromosome structure may accompany this process. However, recent studies based on Hi-C failed to detect these differences. Here we show that global conformational differences are specifically present in the male chromosome X and detectable using Hi-C data on sex-sorted embryos, as well as male and female cell lines, by leveraging custom data analysis solutions. We find the male chromosome X has more mid-/long-range interactions. We also identify differences at structural domain boundaries containing BEAF-32 in conjunction with CP190 or Chromator. Weakening of these domain boundaries in male chromosome X co-localizes with the binding of the dosage compensation complex and its co-factor CLAMP, reported to enhance chromatin accessibility. Together, our data strongly indicate that chromosome X dosage compensation affects global chromosome structure.

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“…The addition of Hi-C increased switch errors in particular by 0.0126 errors/site. This is likely a consequence of somatic chromosome pairing in dipterans ( 30 ), which has previously been demonstrated to create an excess of sister chromosome contacts in Hi-C data ( 9 , 31 ). The increased switch error rate suggests that ∼17% of Illumina-phasable blocks that are joined by the addition of Hi-C result in switch errors.…”

Section: Resultsmentioning

confidence: 97%

One fly–one genome: chromosome-scale genome assembly of a single outbred Drosophila melanogaster

Adams

McBroome

Maurer

et al. 2020

Nucleic Acids Research

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A high quality genome assembly is a vital first step for the study of an organism. Recent advances in technology have made the creation of high quality chromosome scale assemblies feasible and low cost. However, the amount of input DNA needed for an assembly project can be a limiting factor for small organisms or precious samples. Here we demonstrate the feasibility of creating a chromosome scale assembly using a hybrid method for a low input sample, a single outbred Drosophila melanogaster. Our approach combines an Illumina shotgun library, Oxford nanopore long reads, and chromosome conformation capture for long range scaffolding. This single fly genome assembly has a N50 of 26 Mb, a length that encompasses entire chromosome arms, contains 95% of expected single copy orthologs, and a nearly complete assembly of this individual's Wolbachia endosymbiont. The methods described here enable the accurate and complete assembly of genomes from small, field collected organisms as well as precious clinical samples.

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Highly structured homolog pairing reflects functional organization of the Drosophila genome

Cited by 58 publications

References 78 publications

Boundaries potentiate polycomb response element-mediated silencing

Boundaries potentiate polycomb response element-mediated silencing

Global chromatin conformation differences in the Drosophila dosage compensated chromosome X

One fly–one genome: chromosome-scale genome assembly of a single outbred Drosophila melanogaster

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