RNA-seq of HERVK-CRIPRi IPS and iN cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE144151 | GEO | 2020/01/24
REPOSITORIES: GEO
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Project description:Transposable elements (TEs) are key to the evolutionary turnover of regulatory sequences. How they can play such an essential role in spite of their genotoxic potential is unknown. Here, we demonstrate that KRABcontaining zinc finger proteins control the timely and pleiotropic engagement of TE-derived cis-regulators of transcription. We first observed that evolutionary recent TEs of the SVA, HERVK and HERVH subgroups are major contributors to chromatin opening during human embryonic genome activation and act as KLF-stimulated enhancers in naïve embryonic stem cells. We then found that KZFPs of corresponding evolutionary ages are simultaneously induced and repress the transcriptional activity of these TEs. We finally determined that the same KZFP-controlled TE-based enhancers later serve as developmental and tissue-specific regulators of gene expression. Thus, by taming the transcriptional impact of TEs during early embryogenesis, KZFPs allow for their genome-wide incorporation into transcriptional networks, thereby contributing to the species-specificity of human genome regulation.
2019-04-30 | GSE130418 | GEO
Project description:Transposable elements (TEs) are key to the evolutionary turnover of regulatory sequences. How they can play such an essential role in spite of their genotoxic potential is unknown. Here, we demonstrate that KRABcontaining zinc finger proteins control the timely and pleiotropic engagement of TE-derived cis-regulators of transcription. We first observed that evolutionary recent TEs of the SVA, HERVK and HERVH subgroups are major contributors to chromatin opening during human embryonic genome activation and act as KLF-stimulated enhancers in naïve embryonic stem cells. We then found that KZFPs of corresponding evolutionary ages are simultaneously induced and repress the transcriptional activity of these TEs. We finally determined that the same KZFP-controlled TE-based enhancers later serve as developmental and tissue-specific regulators of gene expression. Thus, by taming the transcriptional impact of TEs during early embryogenesis, KZFPs allow for their genome-wide incorporation into transcriptional networks, thereby contributing to the species-specificity of human genome regulation.
2019-04-30 | GSE130417 | GEO
Project description:Transposable elements (TEs) are key to the evolutionary turnover of regulatory sequences. How they can play such an essential role in spite of their genotoxic potential is unknown. Here, we demonstrate that KRABcontaining zinc finger proteins control the timely and pleiotropic engagement of TE-derived cis-regulators of transcription. We first observed that evolutionary recent TEs of the SVA, HERVK and HERVH subgroups are major contributors to chromatin opening during human embryonic genome activation and act as KLF-stimulated enhancers in naïve embryonic stem cells. We then found that KZFPs of corresponding evolutionary ages are simultaneously induced and repress the transcriptional activity of these TEs. We finally determined that the same KZFP-controlled TE-based enhancers later serve as developmental and tissue-specific regulators of gene expression. Thus, by taming the transcriptional impact of TEs during early embryogenesis, KZFPs allow for their genome-wide incorporation into transcriptional networks, thereby contributing to the species-specificity of human genome regulation.
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Project description:Recent work suggests extensive adaptation of transposable elements (TEs) for host gene regulation. However, high numbers of integrations typical of TEs, coupled with sequence divergence within families, have made systematic interrogation of the regulatory contributions of TEs challenging. Here, we employ CARGO, our recent method for CRISPR gRNA multiplexing, to facilitate targeting of LTR5HS, a higher primate-specific class of HERVK (HML-2) LTRs that is active during early development and present in ~700 copies throughout the human genome. We combine CARGO with CRISPR activation or interference to, respectively, induce or silence LTR5HS en masse, and demonstrate that this system robustly targets the vast majority of LTR5HS insertions. Remarkably, activation/silencing of LTR5HS is associated with reciprocal up- and down-regulation of hundreds of human genes. These effects require presence of retroviral sequences, but occur over long genomic distances, consistent with a pervasive function of LTR5HS elements as early embryonic enhancers in higher primates.
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Project description:Recent work suggests extensive adaptation of transposable elements (TEs) for host gene regulation. However, high numbers of integrations typical of TEs, coupled with sequence divergence within families, have made systematic interrogation of the regulatory contributions of TEs challenging. Here, we employ CARGO, our recent method for CRISPR gRNA multiplexing, to facilitate targeting of LTR5HS, a higher primate-specific class of HERVK (HML-2) LTRs that is active during early development and present in ~700 copies throughout the human genome. We combine CARGO with CRISPR activation or interference to, respectively, induce or silence LTR5HS en masse, and demonstrate that this system robustly targets the vast majority of LTR5HS insertions. Remarkably, activation/silencing of LTR5HS is associated with reciprocal up- and down-regulation of hundreds of human genes. These effects require presence of retroviral sequences, but occur over long genomic distances, consistent with a pervasive function of LTR5HS elements as early embryonic enhancers in higher primates.
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Project description:Recent work suggests extensive adaptation of transposable elements (TEs) for host gene regulation. However, high numbers of integrations typical of TEs, coupled with sequence divergence within families, have made systematic interrogation of the regulatory contributions of TEs challenging. Here, we employ CARGO, our recent method for CRISPR gRNA multiplexing, to facilitate targeting of LTR5HS, a higher primate-specific class of HERVK (HML-2) LTRs that is active during early development and present in ~700 copies throughout the human genome. We combine CARGO with CRISPR activation or interference to, respectively, induce or silence LTR5HS en masse, and demonstrate that this system robustly targets the vast majority of LTR5HS insertions. Remarkably, activation/silencing of LTR5HS is associated with reciprocal up- and down-regulation of hundreds of human genes. These effects require presence of retroviral sequences, but occur over long genomic distances, consistent with a pervasive function of LTR5HS elements as early embryonic enhancers in higher primates.
2018-12-19 | GSE124128 | GEO
Project description:The developmental potential of human pluripotent stem cells suggests that they can produce disease-relevant cell types for biomedical research. However, substantial variation has been reported among pluripotent cell lines, which could affect their utility and clinical safety. Such cell-line specific differences must be better understood before one can confidently use embryonic stem (ES) or induced pluripotent stem (iPS) cells in translational research. Towards this goal we have established genome-wide reference maps of DNA methylation and gene expression for 20 previously derived human ES lines and 12 human iPS cell lines, and we have measured the in vitro differentiation propensity of these cell lines. This resource enabled us to assess the epigenetic and transcriptional similarity of ES and iPS cells and to predict the differentiation efficiency of individual cell lines. The combination of assays yields a scorecard for quick and comprehensive characterization of pluripotent cell lines. We used microarrays to compare the gene expression profiles between human ES cell lines, iPS cell lines, fibroblasts and embryoid bodies, and to identify cell-line specific outlier genes. 20 human ES cell lines (HUES1, HUES3, HUES6, HUES8, HUES9, HUES13, HUES28, HUES44, HUES45, HUES48, HUES49, HUES53, HUES62, HUES63, HUES64, HUES65, HUES66, H1, H7, H9), 12 human iPS cell lines (hiPS 11a, hiPS 11b, hiPS 11c, hiPS 15b, hiPS 17a, hiPS 17b, hiPS 18a, hiPS 18b, hiPS 18c, hiPS 20b, hiPS 27b, hiPS 27e), 6 fibroblast cell lines (hFib 11, hFib 15, hFib 17, hFib 18, hFib 20, hFib 27), 5 embryoid bodies (hEB16d HUES1, hEB16d HUES3, hEB16d HUES6, hEB16d HUES45, hEB16d H1)
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