Biology subjects

Alizada, A.

Publications and source records attributed to Alizada, A..

3 recordsLinked to original sources

bioRxiv2024

Ovo is a master regulator of the piRNA pathway in animal ovarian germ cells

The gene-regulatory mechanisms controlling the expression of the germline PIWI- interacting RNA (piRNA) pathway components within the gonads of metazoan species remain largely unexplored. In contrast to the male germline piRNA pathway, which in mice is known to be activated by the testis-specific transcription factor A-MYB, the nature of the ovary-specific gene-regulatory network driving the female germline piRNA pathway remains a mystery. Here, using Drosophila as a model, we combine multiple genomics approaches to reveal the transcription factor Ovo as the master regulator of the germline piRNA pathway in ovaries. The enforced expression of Ovo in somatic cells activates germline piRNA pathway components, including the ping-pong factors Aubergine, Argonaute-3, and Vasa, leading to assembly of peri-nuclear cellular structures resembling nuage bodies of germ cells. Cross-species ChIP-seq and motif analyses demonstrate Ovo binding to genomic CCGTTA motifs within the promoters of germline piRNA pathway genes, suggesting a regulation by Ovo in ovaries analogous to that of A-MYB in testes. Our results also show consistent engagement of the Ovo transcription factor family at ovarian piRNA clusters across metazoan species, reflecting a deep evolutionary conservation of this regulatory paradigm from flies to humans.

molecular biology↗

bioRxiv2023

Promoters of germline transposon silencing genes evolve rapidly accompanied by diverging gene expression

BackgroundThe piRNA pathway in animal gonads functions as an RNA-based immune system, serving to silence transposable elements and prevent inheritance of novel invaders. In Drosophila, this pathway relies on three gonad-specific Argonaute proteins (Argonaute-3, Aubergine and Piwi) that associate with 23-28 nucleotide piRNAs, directing the silencing of transposon-derived transcripts. Transposons constitute a primary driver of genome evolution, yet the evolution of piRNA pathway factors has not received in-depth exploration. Specifically, channel nuclear pore proteins, which impact piRNA processing, exhibit regions of rapid evolution in their promoters. Consequently, the question arises whether such a mode of evolution is a general feature of transposon silencing pathways. ResultsBy employing genomic analysis of coding and promoter regions within genes that function in transposon silencing in Drosophila, we demonstrate that the promoters of germ cell-specific piRNA factors are undergoing rapid evolution. Our findings indicate that rapid promoter evolution is a common trait among piRNA factors engaged in germline silencing across insect species, potentially contributing to gene expression divergence in closely related taxa. Furthermore, we observe that the promoters of genes exclusively expressed in germ cells generally exhibit rapid evolution, with some divergence in gene expression. ConclusionOur results suggest that increased germline promoter evolution, in partnership with other factors, could contribute to transposon silencing and evolution of species through differential expression of genes driven by invading transposons.

evolutionary biology↗

bioRxiv2022

Multi-species analysis of inflammatory response elements reveals ancient and lineage-specific contributions of transposable elements to NF-κB binding

Transposable elements (TEs) provide a source of transcription factor binding sites that can rewire conserved gene regulatory networks. NF-{kappa}B is an evolutionary conserved transcription factor complex primarily involved in innate immunity and inflammation. The extent to which TEs have contributed to NF-{kappa}B responses during mammalian evolution is not well established. Here we performed a multi-species analysis of TEs bound by the NF-{kappa}B subunit RELA (also known as p65) in response to the proinflammatory cytokine TNF. By comparing RELA ChIP-seq data from TNF-stimulated primary aortic endothelial cells isolated from human, mouse and cow, we found that 55 TE subfamilies were associated with RELA bound regions. These RELA-bound transposons possess active epigenetic features and reside near TNF-responsive genes. A prominent example of lineage-specific contribution of transposons comes from the bovine SINE subfamilies Bov-tA1/2/3 which collectively contributed over 14,000 RELA bound regions in cow. By comparing RELA binding data across species, we also found several examples of RELA motif-bearing TEs that colonized the genome prior to the divergence of the three species and contributed to species-specific RELA binding. For example, we found human RELA bound MER81 instances were enriched for the interferon gamma pathway and demonstrated that one RELA bound MER81 element can control the TNF-induced expression of Interferon Gamma Receptor 2 (IFNGR2). Using ancestral reconstructions, we found that RELA containing MER81 instances rapidly decayed during early primate evolution (> 50 million years ago (MYA)) before stabilizing since the separation of Old World monkeys (< 50 MYA). Taken together, our results suggest ancient and lineage-specific transposon subfamilies contributed to mammalian NF-{kappa}B regulatory networks.

genomics↗