Similar Datasets
Project description:LINE1s are abundant retroelements comprising 17% of human genome. Naturally, genomic LINE1s are tightly repressed by epigenetic mechanism; however, if relieved, they can be detrimental to genome stability by their transposition capability. So, a supervising mechanism that quickly re-represses the leaky LINE1s is demanded. Here we show that de-repressed LINE1s generate small RNAs, L1-siRNAs, which SETDB1 and AGO2 recognize, then move into searching for a transcript with sequence complementarity, and ultimately re-install a repression mechanism at LINE1 5’-untranslated region (5’UTR) by depositing trimethyl-H3K9 (H3K9me3). Immunoprecipitation (IP) results showed that SETDB1, AGO2, and L1-siRNA bound to each other and Chromatin-IP-seq and small-RNA-seq results demonstrated that they sat at the same locus within the 5’UTR. SETDB1, AGO2, and L1-siRNA all were necessary for LINE1 repression, particularly the evolutionary young and transposition-competent families such as L1HS/L1PA1 and L1PA2. KAP1, which frequently partners with SETDB1 for silencing local chromatin, was dispensible for the repression of young L1PAs. Our findings indicate that, as a surveillance mechanism, the L1-siRNA-triggered, SETDB1-AGO2-effected repair of epigenetic errors at the 5’UTR establishes a homeostatic re-repression mechanism on inadvertently de-repressed LINE1 copies over the genome.
2023-08-21 | GSE203287 | GEO
Project description:LINE1s are abundant retroelements comprising 17% of human genome. Naturally, genomic LINE1s are tightly repressed by epigenetic mechanism; however, if relieved, they can be detrimental to genome stability by their transposition capability. So, a supervising mechanism that quickly re-represses the leaky LINE1s is demanded. Here we show that de-repressed LINE1s generate small RNAs, L1-siRNAs, which SETDB1 and AGO2 recognize, then move into searching for a transcript with sequence complementarity, and ultimately re-install a repression mechanism at LINE1 5’-untranslated region (5’UTR) by depositing trimethyl-H3K9 (H3K9me3). Immunoprecipitation (IP) results showed that SETDB1, AGO2, and L1-siRNA bound to each other and Chromatin-IP-seq and small-RNA-seq results demonstrated that they sat at the same locus within the 5’UTR. SETDB1, AGO2, and L1-siRNA all were necessary for LINE1 repression, particularly the evolutionary young and transposition-competent families such as L1HS/L1PA1 and L1PA2. KAP1, which frequently partners with SETDB1 for silencing local chromatin, was dispensible for the repression of young L1PAs. Our findings indicate that, as a surveillance mechanism, the L1-siRNA-triggered, SETDB1-AGO2-effected repair of epigenetic errors at the 5’UTR establishes a homeostatic re-repression mechanism on inadvertently de-repressed LINE1 copies over the genome.
2023-08-21 | GSE203286 | GEO
Project description:LINE1s are abundant retroelements comprising 17% of human genome. Naturally, genomic LINE1s are tightly repressed by epigenetic mechanism; however, if relieved, they can be detrimental to genome stability by their transposition capability. So, a supervising mechanism that quickly re-represses the leaky LINE1s is demanded. Here we show that de-repressed LINE1s generate small RNAs, L1-siRNAs, which SETDB1 and AGO2 recognize, then move into searching for a transcript with sequence complementarity, and ultimately re-install a repression mechanism at LINE1 5’-untranslated region (5’UTR) by depositing trimethyl-H3K9 (H3K9me3). Immunoprecipitation (IP) results showed that SETDB1, AGO2, and L1-siRNA bound to each other and Chromatin-IP-seq and small-RNA-seq results demonstrated that they sat at the same locus within the 5’UTR. SETDB1, AGO2, and L1-siRNA all were necessary for LINE1 repression, particularly the evolutionary young and transposition-competent families such as L1HS/L1PA1 and L1PA2. KAP1, which frequently partners with SETDB1 for silencing local chromatin, was dispensible for the repression of young L1PAs. Our findings indicate that, as a surveillance mechanism, the L1-siRNA-triggered, SETDB1-AGO2-effected repair of epigenetic errors at the 5’UTR establishes a homeostatic re-repression mechanism on inadvertently de-repressed LINE1 copies over the genome.
2023-08-21 | GSE203285 | GEO
Project description:LINE1s are abundant retroelements comprising 17% of human genome. Naturally, genomic LINE1s are tightly repressed by epigenetic mechanism; however, if relieved, they can be detrimental to genome stability by their transposition capability. So, a supervising mechanism that quickly re-represses the leaky LINE1s is demanded. Here we show that de-repressed LINE1s generate small RNAs, L1-siRNAs, which SETDB1 and AGO2 recognize, then move into searching for a transcript with sequence complementarity, and ultimately re-install a repression mechanism at LINE1 5’-untranslated region (5’UTR) by depositing trimethyl-H3K9 (H3K9me3). Immunoprecipitation (IP) results showed that SETDB1, AGO2, and L1-siRNA bound to each other and Chromatin-IP-seq and small-RNA-seq results demonstrated that they sat at the same locus within the 5’UTR. SETDB1, AGO2, and L1-siRNA all were necessary for LINE1 repression, particularly the evolutionary young and transposition-competent families such as L1HS/L1PA1 and L1PA2. KAP1, which frequently partners with SETDB1 for silencing local chromatin, was dispensible for the repression of young L1PAs. Our findings indicate that, as a surveillance mechanism, the L1-siRNA-triggered, SETDB1-AGO2-effected repair of epigenetic errors at the 5’UTR establishes a homeostatic re-repression mechanism on inadvertently de-repressed LINE1 copies over the genome.
2023-08-21 | GSE203288 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-10-20 | GSE182198 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-10-11 | GSE86814 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-09-25 | E-GEOD-51138 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-04-02 | GSE102490 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-05-18 | E-GEOD-66526 | biostudies-arrayexpress
Project description:In mammals, RNA interference is primarily a post-transcriptional mechanism. Evidence has accumulated for additional role in transcriptional gene silencing (TGS) but the question for a good paradigm for small interfering antigene RNA (agRNA)-induced chromatin modification remains unanswered. Here, we show that SETDB1, a histone H3-lysine 9 (H3K9)-specific methyltransferase, cooperates with Argonaute-2 (AGO2) and plays an essential role in agRNA-induced TGS. The androgen receptor (AR) gene was transcriptionally silenced by agRNA targeted to its promoter, and we show that this repression was mitigated by knockdown of SETDB1 or AGO2. Chromatin immunoprecipitation demonstrated that agRNA-driven AGO2 was first targeted to the AR promoter, followed by SETDB1. SIN3A and HDAC1/2, the components of the SIN3-HDAC complex, immunoprecipitated with SETDB1, and localized at the agRNA-targeted promoter. Agreeing with the presence of SETDB1, trimethyl-H3K9 was enriched in the AR promoter. Both EZH2 and trimethyl-H3K27 were also present in the targeted locus; accordingly, EZH2 immunoprecipitated with SETDB1. DNA methylation level was not significantly changed, suggesting the absence of de novo methylating activity in agRNA-induced AR promoter. Our results demonstrate that SETDB1, together with AGO2, plays an essential role in TGS through recruiting chromatin remodeler and/or other modifiers, consequently creating a repressive chromatin milieu at the targeted promoter.
| S-EPMC4267665 | biostudies-literature