Multi-omics analysis reveals critical cis-regulatory roles of transposable elements in livestock genomes

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

[1]  Hans H. Cheng,et al.  An atlas of regulatory elements in chicken: A resource for chicken genetics and genomics , 2023, Science advances.

[2]  Heather K. Schmidt,et al.  Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes , 2023, Nature Communications.

[3]  Nakul M. Shah,et al.  Epigenomic analysis reveals prevalent contribution of transposable elements to cis-regulatory elements, tissue-specific expression, and alternative promoters in zebrafish , 2022, Genome research.

[4]  A. Stark,et al.  DeepSTARR predicts enhancer activity from DNA sequence and enables the de novo design of synthetic enhancers , 2022, Nature Genetics.

[5]  M. Georges,et al.  Mapping and analysis of a spatiotemporal H3K27ac and gene expression spectrum in pigs , 2022, Science China Life Sciences.

[6]  Juan M. Vaquerizas,et al.  Zebrafish transposable elements show extensive diversification in age, genomic distribution, and developmental expression , 2022, Genome research.

[7]  J. Murray,et al.  Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors , 2021, bioRxiv.

[8]  Xue You,et al.  PAQR9 regulates hepatic ketogenesis and fatty acid oxidation during fasting by modulating protein stability of PPARα , 2021, Molecular metabolism.

[9]  Shuhong Zhao,et al.  A compendium and comparative epigenomics analysis of cis-regulatory elements in the pig genome , 2021, Nature Communications.

[10]  Kui Li,et al.  SINE jumping contributes to large-scale polymorphisms in the pig genomes , 2021, Mobile DNA.

[11]  Alison L. Van Eenennaam,et al.  Functional annotations of three domestic animal genomes provide vital resources for comparative and agricultural research , 2021, Nature Communications.

[12]  A. Hutchins,et al.  Identifying transposable element expression dynamics and heterogeneity during development at the single-cell level with a processing pipeline scTE , 2021, Nature Communications.

[13]  C. Feschotte,et al.  Evolution of mouse circadian enhancers from transposable elements , 2020, bioRxiv.

[14]  Ting Wang,et al.  Tissue-specific usage of transposable element-derived promoters in mouse development , 2020, Genome biology.

[15]  S. Duncan,et al.  FoxA factors: the chromatin key and doorstop essential for liver development and function , 2020, Genes & development.

[16]  M. Nagasaki,et al.  The Dynamics of Transcriptional Activation by Hepatic Reprogramming Factors. , 2020, Molecular cell.

[17]  Qin Zhang,et al.  PRE-1 Revealed Previous Unknown Introgression Events in Eurasian Boars during the Middle Pleistocene , 2020, Genome biology and evolution.

[18]  G. Cristofari,et al.  Measuring and interpreting transposable element expression , 2020, Nature Reviews Genetics.

[19]  R. D. Hawkins,et al.  Candidate silencer elements for the human and mouse genomes , 2020, Nature Communications.

[20]  Song Li,et al.  DeepTE: a computational method for de novo classification of transposons with convolutional neural network , 2020, bioRxiv.

[21]  Erica C. Pehrsson,et al.  The epigenomic landscape of transposable elements across normal human development and anatomy , 2019, Nature Communications.

[22]  P. Sætrom,et al.  Liver Activation of Hepatocellular Nuclear Factor-4α by Small Activating RNA Rescues Dyslipidemia and Improves Metabolic Profile , 2019, Molecular therapy. Nucleic acids.

[23]  Zuogang Peng,et al.  Evolution and diversity of transposable elements in fish genomes , 2019, Scientific Reports.

[24]  R. Woodfint,et al.  Comparative identification, nutritional, and physiological regulation of chicken liver-enriched genes. , 2019, Poultry science.

[25]  Shuhong Zhao,et al.  Identification and Conservation Analysis of Cis-Regulatory Elements in Pig Liver , 2019, Genes.

[26]  K. Burns,et al.  SQuIRE reveals locus-specific regulation of interspersed repeat expression , 2019, Nucleic acids research.

[27]  Keith A. Crandall,et al.  Telescope: Characterization of the retrotranscriptome by accurate estimation of transposable element expression , 2018, bioRxiv.

[28]  I. Arkhipova Neutral Theory, Transposable Elements, and Eukaryotic Genome Evolution , 2018, Molecular biology and evolution.

[29]  Christopher D. Brown,et al.  Transposable elements generate regulatory novelty in a tissue-specific fashion , 2018, bioRxiv.

[30]  Hua Sun,et al.  TissGDB: tissue-specific gene database in cancer , 2017, Nucleic Acids Res..

[31]  Christopher D. Brown,et al.  Transposable elements are the primary source of novelty in primate gene regulation , 2017, Genome research.

[32]  M. Friberg,et al.  Rapid Increase in Genome Size as a Consequence of Transposable Element Hyperactivity in Wood-White (Leptidea) Butterflies , 2017, Genome biology and evolution.

[33]  Michael C Sachs,et al.  plotROC: A Tool for Plotting ROC Curves. , 2017, Journal of statistical software.

[34]  C. Feschotte,et al.  Co-option of endogenous viral sequences for host cell function. , 2017, Current opinion in virology.

[35]  Alexander Lex,et al.  UpSetR: an R package for the visualization of intersecting sets and their properties , 2017, bioRxiv.

[36]  Thomas Leibing,et al.  GATA4-dependent organ-specific endothelial differentiation controls liver development and embryonic hematopoiesis , 2017, The Journal of clinical investigation.

[37]  C. Feschotte,et al.  Regulatory activities of transposable elements: from conflicts to benefits , 2016, Nature Reviews Genetics.

[38]  Fei Liu,et al.  Transcriptome Analysis Reveals that Vitamin A Metabolism in the Liver Affects Feed Efficiency in Pigs , 2016, G3: Genes, Genomes, Genetics.

[39]  L. Sussel,et al.  Unique functions of Gata4 in mouse liver induction and heart development. , 2016, Developmental biology.

[40]  H. Cui,et al.  The contribution of transposable elements to size variations between four teleost genomes , 2016, Mobile DNA.

[41]  Ying Jin,et al.  TEtranscripts: a package for including transposable elements in differential expression analysis of RNA-seq datasets , 2015, Bioinform..

[42]  Qing-Yu He,et al.  ChIPseeker: an R/Bioconductor package for ChIP peak annotation, comparison and visualization , 2015, Bioinform..

[43]  Edwin Cuppen,et al.  Sambamba: fast processing of NGS alignment formats , 2015, Bioinform..

[44]  G. von Heijne,et al.  Tissue-based map of the human proteome , 2015, Science.

[45]  Fidel Ramírez,et al.  deepTools: a flexible platform for exploring deep-sequencing data , 2014, Nucleic Acids Res..

[46]  K Ito,et al.  Application of ggplot2 to Pharmacometric Graphics , 2013, CPT: pharmacometrics & systems pharmacology.

[47]  Ellen T. Gelfand,et al.  The Genotype-Tissue Expression (GTEx) project , 2013, Nature Genetics.

[48]  G. Bourque,et al.  The Majority of Primate-Specific Regulatory Sequences Are Derived from Transposable Elements , 2013, PLoS genetics.

[49]  Zev N. Kronenberg,et al.  Transposable Elements Are Major Contributors to the Origin, Diversification, and Regulation of Vertebrate Long Noncoding RNAs , 2013, PLoS genetics.

[50]  Petr Novák,et al.  RepeatExplorer: a Galaxy-based web server for genome-wide characterization of eukaryotic repetitive elements from next-generation sequence reads , 2013, Bioinform..

[51]  J. Baker,et al.  Endogenous retroviruses function as species-specific enhancer elements in the placenta , 2013, Nature Genetics.

[52]  R. Slotkin,et al.  Transposable element small RNAs as regulators of gene expression. , 2012, Trends in genetics : TIG.

[53]  Huanming Yang,et al.  The sequence and analysis of a Chinese pig genome , 2012, GigaScience.

[54]  Philip Cayting,et al.  An encyclopedia of mouse DNA elements (Mouse ENCODE) , 2012, Genome Biology.

[55]  Raymond K. Auerbach,et al.  An Integrated Encyclopedia of DNA Elements in the Human Genome , 2012, Nature.

[56]  Steven L Salzberg,et al.  Fast gapped-read alignment with Bowtie 2 , 2012, Nature Methods.

[57]  J. Brosius,et al.  Exonization of transposed elements: A challenge and opportunity for evolution. , 2011, Biochimie.

[58]  Adrian M. Stütz,et al.  A Comprehensive Map of Mobile Element Insertion Polymorphisms in Humans , 2011, PLoS genetics.

[59]  C. Ponting,et al.  Molecular evolution of genes in avian genomes , 2010, Genome Biology.

[60]  C. Glass,et al.  Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. , 2010, Molecular cell.

[61]  Robert C. Edgar,et al.  Characterization and distribution of retrotransposons and simple sequence repeats in the bovine genome , 2009, Proceedings of the National Academy of Sciences.

[62]  Jiuzhou Z. Song,et al.  Calibration of Mutation Rates Reveals Diverse Subfamily Structure of Galliform CR1 Repeats , 2009, Genome biology and evolution.

[63]  G. Ast,et al.  Intronic Alus Influence Alternative Splicing , 2008, PLoS genetics.

[64]  Jiang Qian,et al.  TiGER: A database for tissue-specific gene expression and regulation , 2008, BMC Bioinformatics.

[65]  C. Feschotte Transposable elements and the evolution of regulatory networks , 2008, Nature Reviews Genetics.

[66]  I. K. Jordan,et al.  Origin and Evolution of Human microRNAs From Transposable Elements , 2007, Genetics.

[67]  Christian Biémont,et al.  Genetics: Junk DNA as an evolutionary force , 2006, Nature.

[68]  J. Volff Turning junk into gold: domestication of transposable elements and the creation of new genes in eukaryotes , 2006, BioEssays : news and reviews in molecular, cellular and developmental biology.

[69]  Liane Gagnier,et al.  Retroviral Elements and Their Hosts: Insertional Mutagenesis in the Mouse Germ Line , 2006, PLoS genetics.

[70]  A. Borthakur,et al.  Role of USF1 and USF2 as potential repressor proteins for human intestinal monocarboxylate transporter 1 promoter. , 2005, American journal of physiology. Gastrointestinal and liver physiology.

[71]  Michael Black,et al.  Role of transposable elements in heterochromatin and epigenetic control , 2004, Nature.

[72]  Nansheng Chen,et al.  Using RepeatMasker to Identify Repetitive Elements in Genomic Sequences , 2009, Current protocols in bioinformatics.

[73]  L. N. van de Lagemaat,et al.  Retroelement distributions in the human genome: variations associated with age and proximity to genes. , 2002, Genome research.

[74]  Sudhir Kumar,et al.  Mutation rates in mammalian genomes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[75]  M. Kimura A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences , 1980, Journal of Molecular Evolution.

[76]  C. Goubert Assembly-Free Detection and Quantification of Transposable Elements with dnaPipeTE. , 2023, Methods in molecular biology.

[77]  Ira M. Hall,et al.  BEDTools: a flexible suite of utilities for comparing genomic features , 2010, Bioinform..

[78]  International Human Genome Sequencing Consortium Initial sequencing and analysis of the human genome , 2001, Nature.

[79]  D. Finnegan,et al.  Eukaryotic transposable elements and genome evolution. , 1989, Trends in genetics : TIG.