TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE84460 | GEO | 2016/10/28
SECONDARY ACCESSION(S): PRJNA329247
REPOSITORIES: GEO
Similar Datasets
Project description:BackgroundTen-eleven translocation (TET) enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable elements (TEs), which make up nearly half of the mouse and human genomes. Epigenetic mechanisms controlling TEs have the potential to affect their mobility and to drive the co-adoption of TEs for the benefit of the host.ResultsWe performed a detailed investigation of the role of TET enzymes in the regulation of TEs in mouse embryonic stem cells (ESCs). We find that TET1 and TET2 bind multiple TE classes that harbour a variety of epigenetic signatures indicative of different functional roles. TETs co-bind with pluripotency factors to enhancer-like TEs that interact with highly expressed genes in ESCs whose expression is partly maintained by TET2-mediated DNA demethylation. TETs and 5-hydroxymethylcytosine (5hmC) are also strongly enriched at the 5' UTR of full-length, evolutionarily young LINE-1 elements, a pattern that is conserved in human ESCs. TETs drive LINE-1 demethylation, but surprisingly, LINE-1s are kept repressed through additional TET-dependent activities. We find that the SIN3A co-repressive complex binds to LINE-1s, ensuring their repression in a TET1-dependent manner.ConclusionsOur data implicate TET enzymes in the evolutionary dynamics of TEs, both in the context of exaptation processes and of retrotransposition control. The dual role of TET action on LINE-1s may reflect the evolutionary battle between TEs and the host.
| S-EPMC5116139 | biostudies-literature
Project description:TET enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable elements (TEs), which make up nearly half of the mouse and human genomes. Epigenetic mechanisms controlling TEs have the potential to affect their mobility and to drive the co-adoption of TEs for the benefit of the host. We have performed a detailed investigation of the role of TET enzymes in the regulation of TEs in mouse embryonic stem cells (ESCs). We found that TET1 and TET2 bind multiple TE classes that harbour a variety of epigenetic signatures indicative of different functional roles. Namely, TETs co-bind with pluripotency factors to enhancer-like TEs that interact with highly expressed genes in ESCs, whose expression is partly maintained by the demethylating action of TET2. TETs and 5-hydroxymethylcytosine are also strongly enriched at the 5’ UTR of full-length, evolutionarily young LINE1 elements, a pattern that is conserved in human embryonic stem cells. TET depletion leads to a marked increase in DNA methylation levels at LINE1s, but surprisingly their expression is stably maintained through additional TET-dependent activities. Specifically, we find that TET1 recruits the SIN3A co-repressive complex to LINE1s, ensuring their repression upon TET-driven hypomethylation. This dual nature of TET action may reflect the evolutionary battle between TEs and the host. Our data implicate TET enzymes in the evolutionary dynamics of TEs, both in the context of exaptation processes and of retrotransposition control.
2016-10-28 | GSE84458 | GEO
Project description:TET enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable elements (TEs), which make up nearly half of the mouse and human genomes. Epigenetic mechanisms controlling TEs have the potential to affect their mobility and to drive the co-adoption of TEs for the benefit of the host. We have performed a detailed investigation of the role of TET enzymes in the regulation of TEs in mouse embryonic stem cells (ESCs). We found that TET1 and TET2 bind multiple TE classes that harbour a variety of epigenetic signatures indicative of different functional roles. Namely, TETs co-bind with pluripotency factors to enhancer-like TEs that interact with highly expressed genes in ESCs, whose expression is partly maintained by the demethylating action of TET2. TETs and 5-hydroxymethylcytosine are also strongly enriched at the 5’ UTR of full-length, evolutionarily young LINE1 elements, a pattern that is conserved in human embryonic stem cells. TET depletion leads to a marked increase in DNA methylation levels at LINE1s, but surprisingly their expression is stably maintained through additional TET-dependent activities. Specifically, we find that TET1 recruits the SIN3A co-repressive complex to LINE1s, ensuring their repression upon TET-driven hypomethylation. This dual nature of TET action may reflect the evolutionary battle between TEs and the host. Our data implicate TET enzymes in the evolutionary dynamics of TEs, both in the context of exaptation processes and of retrotransposition control.
2016-10-28 | GSE84459 | GEO
Project description:TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells
| PRJNA329247 | ENA
Project description:TET proteins have been found to play an important role in active demethylation at CpG sites in mammals. There are some reports implicating their functions in removal of DNA methylation imprint at the imprinted regions in the germline. However, it is not well established whether TET proteins can also be involved in demethylation of DNA methylation imprint in embryonic stem (ES) cells. Here we report that loss of TET proteins caused a significant increase in DNA methylation at the Igf2-H19 imprinted region in ES cells. We also observed a variable increase in DNA methylation at the Peg1 imprinted region in the ES clones devoid of TET proteins, in particular in the differentiated ES cells. By contrast, we did not observe a significant increase of DNA methylation imprint at the Peg3, Snrpn and Dlk1-Dio3 imprinted regions in ES cells lacking TET proteins. Interestingly, loss of TET proteins did not result in a significant increase of DNA methylation imprint at the Igf2-H19 and Peg1 imprinted regions in the embryoid bodies (EB). Therefore, TET proteins seem to be differentially involved in maintaining DNA methylation imprint at a subset of imprinted regions in ES cells and EBs.
| S-EPMC4618460 | biostudies-literature
Project description: Not available
| S-EPMC6306448 | biostudies-literature
Project description:Transposable elements (TEs) compose about 40% of the murine genome. Retrotransposition of active TEs such as LINE-1 (L1) tremendously impacts genetic diversification and genome stability. Therefore, transcription and transposition activities of retrotransposons are tightly controlled. Here, we show that the Krüppel-like zinc finger protein Zfp281 directly binds and suppresses a subset of retrotransposons, including the active young L1 repeat elements, in mouse embryonic stem (ES) cells. In addition, we find that Zfp281-regulated L1s are highly enriched for 5-hydroxymethylcytosine (5hmC) and H3K4me3. The COMPASS-like H3K4 methyltransferase Mll2 is the major H3K4me3 methylase at the Zfp281-regulated L1s and required for their proper expression. Our studies also reveal that Zfp281 functions partially through recruiting the L1 regulators DNA hydroxymethylase Tet1 and Sin3A, and restricting Mll2 at these active L1s, leading to their balanced expression. In summary, our data indicate an instrumental role of Zfp281 in suppressing the young active L1s in mouse ES cells.
| S-EPMC5716208 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-12-18 | E-GEOD-52440 | biostudies-arrayexpress
Project description:Enhancer elements control mammalian transcription largely in a cell-type-specific manner. The genome-wide identification of enhancer elements and their activity status in a cellular context is therefore fundamental to understanding cell identity and function. We determined enhancer activity in mouse embryonic stem (ES) cells using chromatin modifications and characterised their global properties. Specifically, we first grouped enhancers into 5 groups using multiple H3K4me1, H3K27ac, and H3K27me3 modification data sets. Active enhancers (simultaneous presence of H3K4me1 and H3K27ac) were enriched for binding of pluripotency factors and were found near pluripotency-related genes. Although both H3K4me1-only and active enhancers were enriched for super-enhancers and a TATA box like motif, active enhancers were preferentially bound by RNA polII (s2) and were enriched for bidirectional transcription, while H3K4me1-only enhancers were enriched for RNA polII (8WG16) suggesting they were likely poised. Bivalent enhancers (simultaneous presence of H3K4me1 and H3K27me3) were preferentially in the vicinity of bivalent genes. They were enriched for binding of components of polycomb complex as well as Tcf3 and Oct4. Moreover, a 'CTTTCTC' de-novo motif was enriched at bivalent enhancers, previously identified at bivalent promoters in ES cells. Taken together, 3 histone modifications successfully demarcated active, bivalent, and poised enhancers with distinct sequence and binding features.
| S-EPMC7876754 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-12-18 | GSE122856 | GEO