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Multi-layer dosage compensation of the avian Z chromosome (single-cell RNA-seq)

ABSTRACT: Multi-layer dosage compensation of the avian Z chromosome (single-cell RNA-seq)

PROVIDER: PRJEB80546 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	ERR13719680_1.fastq.gz	Fastqsanger.gz
	ERR13719680_2.fastq.gz	Fastqsanger.gz

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Multi-layer dosage compensation of the avian Z chromosome (Ribo-seq)

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A male-essential microRNA is key for avian sex chromosome dosage compensation

Project description:Birds have a sex chromosome system in which females are heterogametic (ZW) and males are homogametic (ZZ). The differentiation of avian sex chromosomes from ancestral autosomes entailed the loss of most genes from the W chromosome during evolution. However, to what extent mechanisms evolved that counterbalance the consequences of this extensive gene dosage reduction in female birds has remained unclear. Here we report functional in vivo and evolutionary analyses of a Z-chromosome-linked microRNA (miR-2954) with strongly male-biased expression that was previously proposed to play a key role in sex chromosome dosage compensation1. We knocked out miR-2954 in chicken, which resulted in early embryonic lethality of homozygous knockout males, likely due to the highly specific upregulation of dosage-sensitive Z-linked target genes of miR-2954. Our evolutionary gene expression analyses further revealed that these dosage-sensitive target genes have become upregulated on the single Z in female birds during evolution. Altogether, our work unveils a scenario where evolutionary pressures on females following W gene loss led to the evolution of transcriptional upregulation of dosage-sensitive genes on the Z not only in female but also in male birds. The resulting overabundance of transcripts in males resulting from the combined activity of two dosage-sensitive Z gene copies was in turn offset by the emergence of a highly targeted miR-2954-mediated transcript degradation mechanism during avian evolution. Our findings demonstrate that birds have evolved a unique sex chromosome dosage compensation system in which a microRNA has become essential for male survival.

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Dosage compensation of Z sex chromosome genes in avian fibroblast cells

Project description:Dosage compensation of Z sex chromosome genes in avian fibroblast cells

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Dosage compensation of Z sex chromosome genes in avian fibroblast cells

Project description:Sex in birds is genetically determined, molecular mechanism of which is not well-understood. Their Z sex chromosome (chrZ) lacks whole chromosome inactivation as known for mammalian chrX. To investigate the extent of chrZ dosage compensation and its role in somatic cell’s sex specification, we used a highly-quantitative method and analyzed transcriptional activities of male and female fibroblasts from seven birds. Our data indicate for the first time that ¾ of chrZ genes are strictly compensated, similar to that observed in chrX. We also describe non-compensated chrZ genes and identify Ribosomal Protein S6 (RPS6) as a candidate for universal, sex-dimorphic genes in birds.

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Project description:Studying X-chromosome dosage compensation dynamics in human early embryos using single cell RNA sequencing

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Project description:Gene dosage imbalance of heteromorphic sex chromosomes (XY or ZW) exists between the sexes, and with the autosomes. Mammalian X chromosome inactivation was long thought to imply a critical need for dosage compensation in vertebrates. However, mRNA abundance measurements that demonstrated sex chromosome transcripts are neither balanced between the sexes or with autosomes in monotreme mammals or birds brought sex chromosome dosage compensation into question. This study examines transcriptomic and proteomic levels of dosage compensation in platypus and chicken compared to mouse, a model eutherian species. We analyzed mRNA and protein levels in heart and liver tissues of chicken, mouse and platypus.

2024-07-30 | PXD040182 | Pride

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