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The Drosophila cancer-germline, head-to-head gene pair TrxT and dhd is dispensable for normal brain development but plays a major role in l(3)malignant brain tumour growth.

ABSTRACT: The Drosophila cancer-germline, head-to-head gene pair TrxT and dhd is dispensable for normal brain development but plays a major role in l(3)malignant brain tumour growth.

PROVIDER: PRJNA1095994 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28551767_1.fastq.gz	Fastqsanger.gz
	SRR28551767_2.fastq.gz	Fastqsanger.gz
	SRR28551768.fastq.gz	Fastqsanger.gz
	SRR28551768_1.fastq.gz	Fastqsanger.gz
	SRR28551768_2.fastq.gz	Fastqsanger.gz

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The Drosophila cancer-germline, head-to-head gene pair TrxT and dhd is dispensable for normal brain development but plays a major role in l(3)malignant brain tumour growth.

Project description:Drosophila thioredoxins Deadhead (Dhd) and Thioredoxin-T (TrxT) are encoded by a head-to-head gene pair in the X chromosome. Akin to human cancer-germline (CG) genes, dhd and TrxT expression is normally sex and germline specific, but becomes upregulated in brain tumours of either sex caused by mutation in l(3)malignant brain tumour (l(3)mbt). Using CRISPR/Cas9-mediated knock-out alleles and RNA-seq, we show that while both TrxT and dhd are dispensable for normal brain development, each of them has a significant but partial effect on l(3)mbt brain tumour development as well as on tumour-linked transcriptomic signatures. Moreover, this effect is enhanced by the concomitant removal of both thioredoxins that strongly inhibits l(3)mbt larval brain tumour traits, reduces gene expression differences between tumour and wild-type tissue, and essentially erases all traces of gene expression differences between tumours from larvae of different sex. These results show that TrxT and dhd play a major synergistic role in the emergence of l(3)mbt tumour-linked transcriptomic signatures and tumour development, which is remarkable taking into account that these two genes are never expressed together under normal conditions. We have also found that TrxT is crucial but dhd has no effect on the growth of male-derived l(3)mbt allografts, hence suggesting that the initial stages of tumour development and sustained, long-term tumour growth may depend upon different molecular pathways. In humans, head-to-head inverted gene pairs are abundant among the CG genes that map to the X chromosome, some of which have been shown to work as a unit cancer. Our results identify the first instance of an X-linked, head-to-head CG gene pair in Drosophila and underpin the potential of such CG genes that are dispensable for normal development and homeostasis of somatic tissue, as targets to curtail malignant growth with minimal impact on overall health.

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Project description:In plant pathogenic fungi, conditionally dispensable (CD) chromosomes are often associated with virulence, but not viability. Such virulence-associated CD chromosomes carry genes encoding effectors and/or host-specific toxin biosynthesis enzymes, potentially important for determining host specificity. Fusarium oxysporum causes devastating diseases of more than 100 plant species. In particular, F. oxysporum f. sp. conglutinans (Focn) can infect Brassicaceae plants including Arabidopsis and cabbage. Here we show that Focn has multiple CD chromosomes involving in not only virulence but also vegetative growth, which is an atypical feature of known CD chromosomes. Among them, we identified specific CD chromosomes that are required for virulence to either Arabidopsis, cabbage, or both. We revealed that a pair of effectors encoded in one of the CD chromosomes is required for suppression of the Arabidopsis-specific phytoalexin-based immunity. The effector pair is highly conserved in F. oxysporum isolates capable of infecting Arabidopsis. This study provides insights into how host specificity of F. oxysporum is determined by a pair of effector genes on a CD chromosome.

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