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Multi-layered dosage compensation of the avian Z chromosome by increased transcriptional burst frequency and elevated translational rates

Author

Listed:
  • Natali Papanicolaou

    (Karolinska Institutet)

  • Antonio Lentini

    (Karolinska Institutet)

  • Sebastian Wettersten

    (Karolinska Institutet)

  • Michael Hagemann-Jensen

    (Karolinska Institutet)

  • Annika Krüger

    (Karolinska Institutet)

  • Jilin Zhang

    (Karolinska Institutet)

  • Christos Coucoravas

    (Karolinska Institutet)

  • Ioannis Petrosian

    (Karolinska Institutet)

  • Xian Xin

    (Karolinska Institutet)

  • Ilhan Ceyhan

    (Karolinska Institutet)

  • Joanna Rorbach

    (Karolinska Institutet)

  • Dominic Wright

    (Linköping University)

  • Björn Reinius

    (Karolinska Institutet)

Abstract

Sex-chromosome dosage poses a challenge for heterogametic species in maintaining the proper balance of gene products across chromosomes in each sex. While therian mammals (XX/XY system) achieve near-perfect balance of X-chromosome mRNAs through X-upregulation and X-inactivation, birds (ZW/ZZ system) have been found to lack efficient compensation at RNA level, challenging the necessity of resolving major gene-dosage asymmetries in avian cells. Through comprehensive allele-resolved multiome analyses, we examine dosage compensation in female (ZW), male (ZZ), and rare intersex (ZZW) chicken. Our data reveal that females upregulate their single Z chromosome through increased transcriptional burst frequency, mirroring mammalian X upregulation. Z-protein levels are further balanced in females through enhanced translation efficiency. Additionally, we present a global analysis of promoter elements regulating transcriptional burst kinetics in birds, revealing evolutionary conservation of the genomic encoding of burst kinetics between birds and mammals. Our study provides insights into the regulation of avian dosage compensation, and when considering all regulatory layers collectively, an unexpected similarity between avian and mammalian dosage compensation becomes apparent.

Suggested Citation

  • Natali Papanicolaou & Antonio Lentini & Sebastian Wettersten & Michael Hagemann-Jensen & Annika Krüger & Jilin Zhang & Christos Coucoravas & Ioannis Petrosian & Xian Xin & Ilhan Ceyhan & Joanna Rorbac, 2025. "Multi-layered dosage compensation of the avian Z chromosome by increased transcriptional burst frequency and elevated translational rates," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64817-w
    DOI: 10.1038/s41467-025-64817-w
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    References listed on IDEAS

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    1. repec:plo:pgen00:1007874 is not listed on IDEAS
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    4. Antonio Lentini & Huaitao Cheng & J. C. Noble & Natali Papanicolaou & Christos Coucoravas & Nathanael Andrews & Qiaolin Deng & Martin Enge & Björn Reinius, 2022. "Elastic dosage compensation by X-chromosome upregulation," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
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