Conservation and de novo acquisition of dosage compensation on newly evolved sex chromosomes in <i>Drosophila</i>

Alekseyenko, Artyom A.; Ellison, Chris; Gorchakov, Andrey A.; Zhou, Qi; Kaiser, Vera B.; Toda, Nick; Walton, Zaak; Peng, Shouyong; Park, Peter J.; Bachtrog, Doris; Kuroda, Mitzi I.

doi:10.1101/gad.215426.113

Cited by 63 publications

(104 citation statements)

References 40 publications

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“…Data for D. melanogaster were obtained from mod-ENCODE, and data for H3K27me3, H3K36me3, H3K9me2, and H4K16ac for D. miranda male and female larvae were obtained from Alekseyenko et al (2013) and Zhou et al (2013). To obtain H3K4me1 and H3K4me3 ChIP-seq data, and replicate data for H4K16ac and H3K9m2, we sexed third instar larvae of D. miranda, and followed the protocol of Alekseyenko et al (2013) and Zhou et al (2013) to isolate chromatin and perform ChIP-seq. Briefly, chromatin was isolated from 0.5 g sexed third instar larvae, crosslinked using formaldehyde, and sheared by sonication.…”

Section: Chip-seq Datamentioning

confidence: 99%

The chromatin landscape of Drosophila: comparisons between species, sexes, and chromosomes

Brown

Bachtrog

2014

Genome Res.

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The chromatin landscape is key for gene regulation, but little is known about how it differs between sexes or between species. Here, we study the sex-specific chromatin landscape of Drosophila miranda, a species with young sex chromosomes, and compare it with Drosophila melanogaster. We analyze six histone modifications in male and female larvae of D. miranda (H3K4me1, H3K4me3, H3K36me3, H4K16ac, H3K27me3, and H3K9me2), and define seven biologically meaningful chromatin states that show different enrichments for transcribed and silent genes, repetitive elements, housekeeping, and tissue-specific genes. The genome-wide distribution of both active and repressive chromatin states differs between males and females. In males, active chromatin is enriched on the X, relative to females, due to dosage compensation of the hemizygous X. Furthermore, a smaller fraction of the euchromatic portion of the genome is in a repressive chromatin state in males relative to females. However, sex-specific chromatin states appear not to explain sex-biased expression of genes. Overall, conservation of chromatin states between male and female D. miranda is comparable to conservation between D. miranda and D. melanogaster, which diverged >30 MY ago. Active chromatin states are more highly conserved across species, while heterochromatin shows very low levels of conservation. Divergence in chromatin profiles contributes to expression divergence between species, with~26% of genes in different chromatin states in the two species showing species-specific or species-biased expression, an enrichment of approximately threefold over null expectation. Our data suggest that heteromorphic sex chromosomes in males (that is, a hypertranscribed X and an inactivated Y) may contribute to global redistribution of active and repressive chromatin marks between chromosomes and sexes.

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Section: Chip-seq Datamentioning

confidence: 99%

The chromatin landscape of Drosophila: comparisons between species, sexes, and chromosomes

Brown

Bachtrog

2014

Genome Res.

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“…Within the HASs, a GA-rich sequence motif, the MSL recognition element (MRE), is important for MSL-DCC targeting (Alekseyenko et al 2008;Straub et al 2008). Interestingly, in the related species Drosophila miranda, large autosomal fragments have been fused to a proto-X chromosome relatively recently and are apparently on their way to ''catch up'' with dosage compensation by newly acquiring high-affinity MRE sequences from transposon-derived precursor sequences (Alekseyenko et al 2013;Ellison and Bachtrog 2013).…”

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Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation

et al. 2014

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The male-specific lethal dosage compensation complex (MSL-DCC) selectively assembles on the X chromosome in Drosophila males and activates gene transcription by twofold through histone acetylation. An MSL recognition element (MRE) sequence motif nucleates the initial MSL association, but how it is recognized remains unknown. Here, we identified the CXC domain of MSL2 specifically recognizing the MRE motif and determined its crystal structure bound to specific and nonspecific DNAs. The CXC domain primarily contacts one strand of DNA duplex and employs a single arginine to directly read out dinucleotide sequences from the minor groove. The arginine is flexible when bound to nonspecific sequences. The core region of the MRE motif harbors two binding sites on opposite strands that can cooperatively recruit a CXC dimer. Specific DNA-binding mutants of MSL2 are impaired in MRE binding and X chromosome localization in vivo. Our results reveal multiple dynamic DNA-binding modes of the CXC domain that target the MSL-DCC to X chromosomes.

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“…Indeed, in other Drosophila species with neo-sex chromosomes, dosage compensation was found to evolve rapidly after their formation and degeneration of neo-Y genes, by co-opting the ancestral MSL machinery. In D. miranda, the neo-X chromosome has evolved partial dosage compensation through the acquisition of novel MSL-binding sites that recruit the MSL-complex to the neo-X [14,15], and MSL-binding was found to be associated with H4K16ac enrichment. Even older neo-X chromosomes, like the one shared by members of the D. pseudoobscura subgroup, have evolved full MSL-mediated dosage compensation [3,16].…”

Section: Discussionmentioning

confidence: 99%

“…The neo-X of D. miranda, in contrast, has maintained most of its ancestral genes but is evolving partial dosage compensation, by co-opting the canonical dosage-compensation machinery of Drosophila (the MSL-complex). This complex is targeted to the ancestral X of Drosophila species, and up-regulates gene expression through changes of the chromatin conformation of the X, mediated by histone H4 lysine 16 acetylation (H4K16ac) [14,15]. The neo-sex chromosome shared by members of the D. pseudoobscura species group was formed about 15 million years ago, and has evolved the typical properties of old sex chromosomes: the neo-Y is completely degenerate and heterochromatic, while the neo-X is fully dosage compensated by the MSL machinery [3,16].…”

Section: Introductionmentioning

confidence: 99%

Ancestral chromatin configuration constrains chromatin evolution on differentiating sex chromosomes in Drosophila

Zhou

Bachtrog

2015

Preprint

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Sex chromosomes evolve distinctive types of chromatin from a pair of ancestral autosomes that are usually euchromatic. In Drosophila, the dosage-compensated X becomes enriched for hyperactive chromatin in males (mediated by H4K16ac), while the Y chromosome acquires silencing heterochromatin (enriched for H3K9me2/3). Drosophila autosomes are typically mostly euchromatic but the small dot chromosome has evolved a heterochromatinlike milieu (enriched for H3K9me2/3) that permits the normal expression of dot-linked genes, but which is different from typical pericentric heterochromatin. In Drosophila busckii, the dot chromosomes have fused to the ancestral sex chromosomes, creating a pair of 'neo-sex' chromosomes. Here we collect genomic, transcriptomic and epigenomic data from D. busckii, to investigate the evolutionary trajectory of sex chromosomes from a largely heterochromatic ancestor. We show that the neo-sex chromosomes formed <1 million years ago, but nearly 60% of neo-Y linked genes have already become non-functional. Expression levels are generally lower for the neo-Y alleles relative to their neo-X homologs, and the silencing heterochromatin mark H3K9me2, but not H3K9me3, is significantly enriched on silenced neo-Y genes. Despite rampant neo-Y degeneration, we find that the neo-X is deficient for the canonical histone modification mark of dosage compensation (H4K16ac), relative to autosomes or the compensated ancestral X chromosome, possibly reflecting constraints imposed on evolving hyperactive chromatin in an originally heterochromatic environment. Yet, neo-X genes are transcriptionally more active in males, relative to females, suggesting the evolution of incipient dosage compensation on the neo-X. Our data show that Y degeneration proceeds quickly after sex chromosomes become established through genomic and epigenetic changes, and are consistent with the idea that the evolution of sex-linked chromatin is influenced by its ancestral configuration. Data Availability Statement: All sequencing reads, the genome sequence assembly and annotation generated in this study are deposited at the National Center for Biotechnology Information Short Reads Archive (www.ncbi.nlm.nih.gov/sra) under the Bioproject accession no. PRJNA274996.Funding: This work was funded by NIH grants (R01GM076007, R01GM093182 and R01GM101255) to DB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author SummaryDNA is packaged with proteins into two general types of chromatin: the transcriptionally active euchromatin and repressive heterochromatin. Sex chromosomes typically evolve from a pair of euchromatic autosomes. The Y chromosome of Drosophila is gene poor and almost entirely heterochromatic; the X chromosome, in contrast, has evolved a hyperactive euchromatin structure and globally up-regulates its gene expression, to compensate for loss of activity from the homologous genes on the Y chromosome. The evolutionary trajectory along which sex chromosomes...

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Conservation and de novo acquisition of dosage compensation on newly evolved sex chromosomes in Drosophila

Cited by 63 publications

References 40 publications

The chromatin landscape of Drosophila: comparisons between species, sexes, and chromosomes

The chromatin landscape of Drosophila: comparisons between species, sexes, and chromosomes

Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation

Ancestral chromatin configuration constrains chromatin evolution on differentiating sex chromosomes in Drosophila

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