Multi-omics analysis reveals critical cis-regulatory roles of transposable elements in livestock genomes DOI Creative Commons
Chao Wang,

Bowen Lei,

Yongzhou Bao

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 17, 2023

Abstract As a major source of genetic and regulatory variation in their host genome, transposable elements (TEs) have gained growing interest research on humans model organisms. In this species, integrative analysis multi-omics data has shed light the functions TEs. However, there remains notable gap our understanding TEs domesticated animals. we annotated genomes pigs, cattle, chickens, respectively, systematically compared genome distributions amplification patterns across these three species. Furthermore, by integrating multi-tissue RNA-seq, ATAC-seq, histone modification ChIP-seq data, explored expression atlas contribution to cis-regulatory (CREs) different tissues Most importantly, developed novel computational framework that revealed TE-mediated gene networks (TE-GRNs) underlying tissue-related biological processes. To demonstrate power approach, applied analyze liver Overall, provides insights into livestock animals highlights uncover TE-GRNs various contexts.

Language: Английский

Cryptic endogenous retrovirus subfamilies in the primate lineage DOI Creative Commons
Xun Chen, Zicong Zhang,

Yi-Zhi Yan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 8, 2023

ABSTRACT Many endogenous retroviruses (ERVs) in the human genome are primate-specific and have contributed novel cis-regulatory elements transcripts. However, current approaches for classifying annotating ERVs their long terminal repeats (LTRs) limited resolution inaccurate. Here, we developed a new annotation based on phylogenetic analysis cross-species conservation. Focusing evolutionary young MER11A/B/C subfamilies, revealed presence of 4 ‘new subfamilies’, that better explained epigenetic heterogeneity observed within MER11 instances, suggesting 412 (19.8%) these repeat elements. Furthermore, functionally validated regulatory potential four subfamilies using massively parallel reporter assay (MPRA), which also identified motifs associated with differential activities. Combining MPRA annotations across primates an apes-specific gain SOX related through single-nucleotide deletion. Lastly, by applying our approach 53 simian-enriched LTR defined total 75 found 3,807 (30.0%) instances from 26 could be categorized into annotation, many distinct profile. Thus, refined LTRs, it will possible to understand evolution primate genomes potentially identify roles LTRs hosts.

Language: Английский

Citations

3
Transposable elements may enhance antiviral resistance in HIV-1 elite controllers DOI Creative Commons
Manvendra Singh, Sabrina M. Leddy, L. Iñiguez

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 12, 2023

Less than 0.5% of people living with HIV-1 are elite controllers (ECs) - individuals who have a replication-competent viral reservoir in their CD4

Language: Английский

Citations

2
Intrinsically linked lineage-specificity of transposable elements and lncRNAs reshapes transcriptional regulation species- and tissue-specifically DOI Open Access
Jie Lin, Yijin Wu, Sha He

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 7, 2024

Abstract Lineage-specificity of transcriptional regulation by lncRNAs critically determines whether mouse models reliably mimic human diseases. To address this question, we identified human/mouse-specific from GENCODE-annotated and lncRNAs, predicted their DNA binding domains (DBDs) sites (DBSs), analysed transposable elements (TEs) in DBDs DBSs, functional enrichment target genes. 84%/98% 61%/95% DBDs, 46%/73% DBSs contain TEs almost exclusively originated simians/rodents, indicating intrinsically linked lineage-specificity TEs, lncRNAs’ DBSs. We then revealed how is lineage-specifically rewired co-opted analysing distributions genes signalling pathways expression multiple tissues humans mice. Transcriptional greatly species-specifically tissue-specifically. further transcriptomic data Alzheimer’s disease tumours patients models, with results supporting the above conclusions. Our reveal elements, regulation, provide tool for differentiating mice, suggest that many evolutionary novelties may be destined to lineage-specific.

Language: Английский

Citations

0
Gene ontology-guided proximity placement analyses of pan-primate regulatory LTR elements that contribute to embryogenesis. DOI Creative Commons
Gennadi V. Glinsky

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 13, 2024

Abstract Two distinct families of pan-primate endogenous retroviruses, namely HERVL and HERVH, infected primates germline, colonized host genomes, evolved into the global genomic regulatory dominion (GRD) operating during human embryogenesis (HE). Analyzed in this contribution GRD derived from HERV sequences constitutes 8839 highly conserved fixed LTR elements linked to 5444 down-stream target genes forged by evolution a functionally-consonant constellation 26 genome-wide multimodular networks (GRNs), each which is defined significant enrichment numerous single gene ontology (GO)-specific traits. Locations GRNs appear scattered across chromosomes occupy 5.5%-15.09% genome. Each GRN harbors 529-1486 LTRs LTR7, MLT2A1, MLT2A2 that quantitatively balanced according their abundance. integrate activities 199-805 genes, including transcription factors, chromatin-state remodelers, signal-sensing signal-transduction mediators, enzymatic receptor binding effectors, intracellular complexes extracellular matrix elements, cell-cell adhesion molecules. compositions consist several hundred thousands smaller GO enrichment-defined modules (GRMs) combining dozen hundreds operate on individuals life-span timescale along specific phenotypic avenues exert profound effects patterns transcription, protein-protein interactions, developmental phenotypes, physiological traits, pathological conditions Modern Humans. Overall, study identifies 69,573 statistically LTR-linked GRMs (Binominal FDR q-value threshold 0.001), 27,601 validated GO-specific directed acyclic graph (DAG) analyses six annotations. Collectively, reported herein observations support hypothesis ERVs have made impacts affecting traits Humans, phenotypes manifestation considered human-specific.

Language: Английский

Citations

0
The role of transposable elements in human evolution and methods for their functional analysis: current status and future perspectives DOI Creative Commons
Kei Fukuda

Genes & Genetic Systems, Journal Year: 2023, Volume and Issue: 98(6), P. 289 - 304

Published: Oct. 19, 2023

Transposable elements (TEs) are mobile DNA sequences that can insert themselves into various locations within the genome, causing mutations may provide advantages or disadvantages to individuals and species. The insertion of TEs result in genetic variation affect a wide range human traits including disorders. Understanding role biology is crucial for both evolutionary medical research. This review discusses involvement disease susceptibility, as well methods functional analysis TEs.

Language: Английский

Citations

1
Mini-heterochromatin domains constrain thecis-regulatory impact of SVA transposons in human brain development and disease DOI Creative Commons
Vivien Horváth, Raquel Garza, Marie E. Jönsson

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 21, 2023

Abstract SVA retrotransposons remain active in humans and contribute to individual genetic variation. Polymorphic alleles harbor gene-regulatory potential can cause disease. However, how insertions are controlled functionally impact human disease is unknown. Here, we dissect the epigenetic regulation influence of SVAs cellular models X-linked dystonia-parkinsonism (XDP), a neurodegenerative disorder caused by an insertion at TAF1 locus. We demonstrate that KRAB zinc finger protein ZNF91 establishes H3K9me3 DNA methylation over SVAs, including polymorphic alleles, neural progenitor cells. The resulting mini-heterochromatin domains attenuate cis -regulatory SVAs. This critical for XDP pathology; removal local heterochromatin severely aggravates molecular phenotype, increased intron retention reduced expression. Our results provide unique mechanistic insights into transposon recognized, their regulatory constrained innate defense system.

Language: Английский

Citations

1
Multi-omics analysis reveals critical cis-regulatory roles of transposable elements in livestock genomes DOI Creative Commons
Chao Wang,

Bowen Lei,

Yongzhou Bao

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 17, 2023

Abstract As a major source of genetic and regulatory variation in their host genome, transposable elements (TEs) have gained growing interest research on humans model organisms. In this species, integrative analysis multi-omics data has shed light the functions TEs. However, there remains notable gap our understanding TEs domesticated animals. we annotated genomes pigs, cattle, chickens, respectively, systematically compared genome distributions amplification patterns across these three species. Furthermore, by integrating multi-tissue RNA-seq, ATAC-seq, histone modification ChIP-seq data, explored expression atlas contribution to cis-regulatory (CREs) different tissues Most importantly, developed novel computational framework that revealed TE-mediated gene networks (TE-GRNs) underlying tissue-related biological processes. To demonstrate power approach, applied analyze liver Overall, provides insights into livestock animals highlights uncover TE-GRNs various contexts.

Language: Английский

Citations

0