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Locus-specific chromatin profiling of evolutionarily young transposable elements [Hi-C]

ABSTRACT: Despite a vast expansion in the availability of epigenomic data, our knowledge of the chromatin landscape at interspersed repeats remains highly limited by difficulties in mapping short-read sequencing data to these regions. In particular, little is known about the locus-specific regulation of evolutionarily young transposable elements (TEs), which have been implicated in genome stability, gene regulation and innate immunity in a variety of developmental and disease contexts. Here we propose an approach for generating locus-specific protein-DNA binding profiles at interspersed repeats, which leverages information on the spatial proximity between repetitive and non-repetitive genomic regions. We demonstrate that the combination of Hi-ChIP and a newly developed mapping tool (PAtChER) yields accurate protein enrichment profiles at individual repetitive loci. Using this approach, we show that young TEs display locus- and tissue-specific chromatin profiles in both mice and humans. Insights gained using our method will be invaluable for dissecting the molecular determinants of TE regulation and their impact on the genome.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE182305 | GEO | 2021/08/19

REPOSITORIES: GEO

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Locus-specific chromatin profiling of evolutionarily young transposable elements [HiChIP]

Project description:Despite a vast expansion in the availability of epigenomic data, our knowledge of the chromatin landscape at interspersed repeats remains highly limited by difficulties in mapping short-read sequencing data to these regions. In particular, little is known about the locus-specific regulation of evolutionarily young transposable elements (TEs), which have been implicated in genome stability, gene regulation and innate immunity in a variety of developmental and disease contexts. Here we propose an approach for generating locus-specific protein-DNA binding profiles at interspersed repeats, which leverages information on the spatial proximity between repetitive and non-repetitive genomic regions. We demonstrate that the combination of Hi-ChIP and a newly developed mapping tool (PAtChER) yields accurate protein enrichment profiles at individual repetitive loci. Using this approach, we show that young TEs display locus- and tissue-specific chromatin profiles in both mice and humans. Insights gained using our method will be invaluable for dissecting the molecular determinants of TE regulation and their impact on the genome.

2021-08-19 | GSE182304 | GEO

Control of agricultural traits by hc-siRNA associated MITEs in rice

Project description:Transposable elements (TEs) and repetitive sequences comprise over 40% of rice genome. Different TEs are tightly regulated by distinct epigenetic mechanisms. For example, the activities of LTR retrotransposon Tos17 and non-LTR retrotransposon LINE element Karma are uniquely regulated by histone H3K9 methylation and histone H3K4 demethylation, respectively. Miniature inverted repeat transposable elements (MITEs) are one of the most high-copy-number DNA transposons, which are interspersed around rice genome and might influence nearby gene expression. In plants, 24-nucleotide (24-nt) heterochromatic small interfering RNAs (hc-siRNAs) derived from repeats and TEs. To what extent hc-siRNA associated TEs affect gene expression and therefore contribute to agricultural traits in rice remains elusive. Here, we show that OsDCL3a, one of Dicer-Like 3 (DCL3) homolog, is primarily responsible for 24-nt hc-siRNA processing in rice. Impaired OsDCL3a displayed altered important agricultural traits in rice. We found that genome-wide (281,563) 24-nt hc-siRNA clusters were OsDCL3a-dependent, among which MITEs were significantly enriched. Impaired OsDCL3a caused significant overlapping between reduced hc-siRNAs from MITEs and elevated nearby gene expression. Intriguingly, genes involved in Gibberellin and Brassinosteroid homeostasis were identified as direct targets of OsDCL3a, which may attribute to dwarfism and enlarged flag leaf angle upon OsDCL3a deficiency. Our work uncovers OsDCL3a-dependent hc-siRNAs derived from MITEs as broad spectrum of regulators for fine-tuning gene expression, and this observation may reflect a conserved mechanism in other higher plants with dispersed repeat- or TE-rich genomes. Examination of OsDCL3a-dependent hc-siRNAs derived from MITEs.

2014-02-04 | E-GEOD-50778 | biostudies-arrayexpress

Transposable element expression at unique loci in single cells with CELLO-seq

Project description:We introduce a novel method (CELLO-seq) for long-read RNA sequencing at single cell resolution. CELLO-seq allows for full-length RNA sequencing and enables measurement of allelic, isoform and Transposable Element (TE) expression at unique loci. We use CELLO-seq to assess the widespread expression of TEs in 2-cell mouse blastomeres as well as human induced pluripotent stem cells (hiPSCs). Across both species, old and young TEs showed evidence of locus-specific expression, with simulations demonstrating that only a small number of very young elements in the mouse could not be mapped back to with high confidence. Exploring the relationship between the expression of individual elements and putative regulators revealed surprising heterogeneity, with TEs within a class showing different patterns of correlation, suggesting distinct regulatory mechanisms. CELLO-seq thus represents a significant advance in the research of TEs, highlighting that studying TEs in single cells and at single loci resolution is necessary for understanding how such elements are regulated and for gaining insight into their role during development.

2020-10-01 | E-MTAB-9577 | biostudies-arrayexpress

Control of agricultural traits by hc-siRNA associated MITEs in rice

2014-02-04 | GSE50778 | GEO

Combinatorial DNA methylation codes at repetitive elements [ChIP-Seq]

Project description:DNA methylation is an essential epigenetic modification, present in both unique DNA sequences and repetitive elements, but its exact function in repetitive elements remains obscure. Here, we describe the genome-wide comparative analysis of the 5mC, 5hmC, 5fC and 5caC profiles of repetitive elements in mouse embryonic fibroblasts and mouse embryonic stem cells. We provide evidence for distinct and highly specific DNA methylation/oxidation patterns of the repetitive elements in both cell types, which mainly affect CA repeats and evolutionary conserved mouse-specific transposable elements including IAP-LTRs, SINEs B1m/B2m and L1Md-LINEs. DNA methylation controls the expression of these retro-elements, which are clustered at specific locations in the mouse genome. We show that TDG is implicated in the regulation of their unique DNA methylation/oxidation signatures and their dynamics. Our data suggest the existence of novel epigenetic code for the most recently acquired evolutionary conserved repeats that could play a major role in cell differentiation.

2017-02-22 | GSE77767 | GEO

Combinatorial DNA methylation codes at repetitive elements

2017-02-22 | GSE66438 | GEO

Combinatorial DNA methylation codes at repetitive elements [RNA-Seq]

2017-02-22 | GSE77769 | GEO

Combinatorial DNA methylation codes at repetitive elements [MeDIP-Seq]

2017-02-22 | GSE77768 | GEO

A map of mobile DNA insertions in the NCI-60 human cancer cell panel

Project description:The National Cancer Institute-60 (NCI-60) cell lines are among the most widely used models of human cancer. They provide a platform to integrate DNA sequence information, epigenetic data, RNA and protein expression, and pharmacologic susceptibilities in studies of cancer cell biology. Genome-wide studies of the NCI-60 have included exome sequencing, karyotyping, and copy number analyses but have not targeted repetitive sequences. Interspersed repeats are a significant source of heritable genetic variation, and insertions of active elements can occur somatically in malignancy. To approach a functional understanding of these sequences in transformed cells, we used transposon insertion profiling (TIP) to map Long INterspersed Element-1 (LINE-1, L1) and Alu Short INterspersed Element (SINE) insertions in cancer genes in NCI-60 cells. As expected, this identified known insertions, polymorphisms shared in unrelated tumor cell lines, as well as unique, potentially tumor-specific insertions. Here, we report a map of these insertion sites and conduct association analyses relating individual insertions to a variety of cellular phenotypes.

2017-02-09 | GSE83756 | GEO

Epigenome editing of microsatellite repeat enhancers reveals specific regulatory functions and tumor dependencies [NRO-Seq]

Project description:Various types of repetitive sequences are dysregulated in cancer but their contributions to oncogenesis are yet to be determined. Here we combine nascent transcription profiling with epigenome editing to test the function of GGAA microsatellites in Ewing sarcoma, a pediatric bone cancer where the oncogenic fusion protein EWS-FLI1 induces chromatin features of active enhancers at this class of repeats. Silencing of chromatin through epigenome editing at specific GGAA repeats abolished local nascent transcription, decreased the expression of neighboring target genes and, in the case of a repeat associated with the SOX2 locus, reduced the growth of tumor xenografts. Our studies directly demonstrate that repeat elements can acquire enhancer functions in cancer and become critical components of oncogenic gene regulation programs.

2018-07-30 | GSE106915 | GEO

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