MSL3 coordinates a transcriptional and translational meiotic program in female Drosophila

McCarthy, Alicia; Sarkar, Kahini; Martin, Elliot T.; Upadhyay, Maitreyi; James, Joshua R.; Lin, Jennifer M.; Jang, Seoyeon; Williams, Nathan D.; Forni, Paolo E.; Rangan, Prashanth

doi:10.1101/2019.12.18.879874

Cited by 5 publications

(10 citation statements)

References 168 publications

(14 reference statements)

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“…In our scRNA-seq data, no DCC genes were enriched in germ cells except msl-3 and Clamp, which were enriched in GSC/early spermatogonia (Fig 4A). Rather than acting on dosage compensation, msl-3 might instead be facilitating entry into meiosis, as suggested by recent work in mice [28]. If so, this could suggest a conserved function of msl-3 across kingdoms and explain the lack of germline enrichment of any other DCC genes in our data.…”

Section: Discussionsupporting

confidence: 53%

Single-cell RNA-sequencing reveals pre-meiotic X-chromosome dosage compensation in Drosophila testis

et al. 2021

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Dosage compensation equalizes X-linked expression between XY males and XX females. In male fruit flies, expression levels of the X-chromosome are increased approximately two-fold to compensate for their single X chromosome. In testis, dosage compensation is thought to cease during meiosis; however, the timing and degree of the resulting transcriptional suppression is difficult to separate from global meiotic downregulation of each chromosome. To address this, we analyzed testis single-cell RNA-sequencing (scRNA-seq) data from two Drosophila melanogaster strains. We found evidence that the X chromosome is equally transcriptionally active as autosomes in somatic and pre-meiotic cells, and less transcriptionally active than autosomes in meiotic and post-meiotic cells. In cells experiencing dosage compensation, close proximity to MSL (male-specific lethal) chromatin entry sites (CES) correlates with increased X chromosome transcription. We found low or undetectable levels of germline expression of most msl genes, mle, roX1 and roX2 via scRNA-seq and RNA-FISH, and no evidence of germline nuclear roX1/2 localization. Our results suggest that, although dosage compensation occurs in somatic and pre-meiotic germ cells in Drosophila testis, there might be non-canonical factors involved in the dosage compensation mechanism. The single-cell expression patterns and enrichment statistics of detected genes can be explored interactively in our database: https://zhao.labapps.rockefeller.edu/gene-expr/.

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Section: Discussionsupporting

confidence: 53%

Single-cell RNA-sequencing reveals pre-meiotic X-chromosome dosage compensation in Drosophila testis

et al. 2021

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“…In Drosophila , both sexes express MOF and MLE proteins ( Fig 1G and H [ Kotlikova et al, 2006 ; Conrad et al, 2012 ]), and at least in some tissues, MSL1 and MSL3 are not only present in males, but also in females ( Chlamydas et al, 2016 ; McCarthy et al, 2019 Preprint ). However, posttranscriptional mechanisms prevent MSL2 protein expression in females thereby providing the DC function specifically to males ( Beckmann et al, 2005 ).…”

Section: Resultsmentioning

confidence: 99%

Distinct mechanisms mediate X chromosome dosage compensation in Anopheles and Drosophila

et al. 2021

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Sex chromosomes induce potentially deleterious gene expression imbalances that are frequently corrected by dosage compensation (DC). Three distinct molecular strategies to achieve DC have been previously described in nematodes, fruit flies, and mammals. Is this a consequence of distinct genomes, functional or ecological constraints, or random initial commitment to an evolutionary trajectory? Here, we study DC in the malaria mosquito Anopheles gambiae. The Anopheles and Drosophila X chromosomes evolved independently but share a high degree of homology. We find that Anopheles achieves DC by a mechanism distinct from the Drosophila MSL complex–histone H4 lysine 16 acetylation pathway. CRISPR knockout of Anopheles msl-2 leads to embryonic lethality in both sexes. Transcriptome analyses indicate that this phenotype is not a consequence of defective X chromosome DC. By immunofluorescence and ChIP, H4K16ac does not preferentially enrich on the male X. Instead, the mosquito MSL pathway regulates conserved developmental genes. We conclude that a novel mechanism confers X chromosome up-regulation in Anopheles. Our findings highlight the pluralism of gene-dosage buffering mechanisms even under similar genomic and functional constraints.

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“…Ovaries from flies were dissected in cold 1x PBS. RNA was isolated using TRIzol (Invitrogen, 15596026) (Blatt et al, 2021;McCarthy et al, 2019).…”

Section: Rna Isolationmentioning

confidence: 99%

A feedback loop between heterochromatin and the nucleopore complex controls germ-cell to oocyte transition duringDrosophilaoogenesis

Sarkar

Kotb

Lemus

et al. 2021

Preprint

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SummaryGerm cells differentiate into oocytes that become totipotent upon fertilization. How the highly specialized oocyte acquires this distinct cell fate is poorly understood. During Drosophila oogenesis, H3K9me3 histone methyltransferase SETDB1 translocates from the cytoplasm to the nucleus of germ cells concurrent with oocyte specification. Here, we discovered that nuclear SETDB1 is required to silence a cohort of differentiation-promoting genes by mediating their heterochromatinization. Intriguingly, SETDB1 is also required for the upregulation of 18 of the ~30 nucleoporins (Nups) that comprise the nucleopore complex (NPC). NPCs in turn anchor SETDB1-dependent heterochromatin at the nuclear periphery to maintain H3K9me3 and gene silencing in the egg chambers. Aberrant gene expression due to loss of SETDB1 or Nups results in loss of oocyte identity, cell death and sterility. Thus, a feedback loop between heterochromatin and NPCs promotes transcriptional reprogramming at the onset of oocyte specification that is critical to establish oocyte identity.

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MSL3 coordinates a transcriptional and translational meiotic program in female Drosophila

Cited by 5 publications

References 168 publications

Single-cell RNA-sequencing reveals pre-meiotic X-chromosome dosage compensation in Drosophila testis

Single-cell RNA-sequencing reveals pre-meiotic X-chromosome dosage compensation in Drosophila testis

Distinct mechanisms mediate X chromosome dosage compensation in Anopheles and Drosophila

A feedback loop between heterochromatin and the nucleopore complex controls germ-cell to oocyte transition duringDrosophilaoogenesis

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