Sex-specific splicing occurs genome-wide during early Drosophila embryogenesis

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Data availability
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Abstract

Sex-specific splicing is an essential process that regulates sex determination and drives sexual dimorphism. Yet, how early in development widespread sex-specific transcript diversity occurs was unknown because it had yet to be studied at the genome-wide level. We use the powerful Drosophila model to show that widespread sex-specific transcript diversity occurs early in development, concurrent with zygotic genome activation. We also present a new pipeline called time2splice to quantify changes in alternative splicing over time. Furthermore, we determine that one of the consequences of losing an essential maternally-deposited pioneer factor called CLAMP (Chromatin linked adapter for MSL proteins) is altered sex-specific splicing of genes involved in diverse biological processes that drive development. Overall, we show that sex-specific differences in transcript diversity exist even at the earliest stages of development.

Data availability

Sequencing data have been deposited in GEO under accession codes #GSE220455 and #GSE220439All data generated or analyzed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 2-figure Supplement 3, Figure 5, and Figure 6Source data used to generate all the figures, graphs, and Venn diagrams are provided in Supplementary Data Tables S1-S7

The following data sets were generated

(2022) Effect of loss of transcription factor CLAMP on sex-specific splicing in Drosophila third instar larvae (L3) stage
NCBI Gene Expression Omnibus, GSE220455.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE220455
(2022) Identifying splicing targets of CLAMP by mRNA-sequencing
NCBI Gene Expression Omnibus, GSE220439.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE220439

The following previously published data sets were used

1. Rieder LE
2. Koreski KP
3. Boltz KA
4. Kuzu G
5. Urban JA
6. Bowman S
7. Zeidman A
8. Jordan III WT
9. Tolstorukov MY
10. Marzluff WF
11. Duronio RJ
12. Larschan EN
(2017) Histone locus regulation by the Drosophila dosage compensation adaptor protein CLAMP
NCBI Gene Expression Omnibus, GSE102922.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi
(2019) Targeting of the dosage-compensated male X-chromosome during early Drosophila development
NCBI Gene Expression Omnibus, GSE133637.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi
1. Moschall R
2. Rossbach O
3. Lehmann G
4. Kullmann L
5. Eichner N
6. Strauss D
7. Strieder N
8. Meister G
9. Krahn M
10. Medenbach J
(2019) Flipping the switch on Sex-lethal expression: Sister of Sex-lethal antagonizes Sxl-dependent alternative splicing to maintain a male-specific gene expression pattern in Drosophila (RIP-Seq)
NCBI Gene Expression Omnibus, GSE98187.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi

Article and author information

Author details

Mukulika Ray

Molecular Biology, Cellular Biology and Biochemistry Department, Brown University, Providence, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9064-818X
Ashley Mae Conard

Center for Computational Molecular Biology, Brown University, Providence, United States

Competing interests
The authors declare that no competing interests exist.
Jennifer Urban

Biology Department, Johns Hopkins University, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6621-8358
Pranav Mahableshwarkar

Center for Computational Molecular Biology, Brown University, Providence, United States

Competing interests
The authors declare that no competing interests exist.
Joseph Aguilera

Molecular Biology, Cellular Biology and Biochemistry Department, Brown University, Providence, United States

Competing interests
The authors declare that no competing interests exist.
Annie Huang

Molecular Biology, Cellular Biology and Biochemistry Department, Brown University, Providence, United States

Competing interests
The authors declare that no competing interests exist.
Smriti Vaidyanathan

Center for Computational Molecular Biology, Brown University, Providence, United States

Competing interests
The authors declare that no competing interests exist.
Erica Larschan

Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, United States

For correspondence
erica_larschan@brown.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2484-4921

Funding

National Institute of General Medical Sciences (R35GM126994)

Mukulika Ray
Erica Larschan

National Science Foundation (Graduate Research Fellowship)

Ashley Mae Conard

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.