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DNMT1 in Six2 progenitor cells is essential for transposable element silencing and kidney development

ABSTRACT: DNMT1 in Six2 progenitor cells is essential for transposable element silencing and kidney development

PROVIDER: PRJNA433843 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6709940.fastq.gz	Fastqsanger.gz
	SRR6709950_1.fastq.gz	Fastqsanger.gz
	SRR6709950_2.fastq.gz	Fastqsanger.gz
	SRR6709941.fastq.gz	Fastqsanger.gz
	SRR6709951_1.fastq.gz	Fastqsanger.gz

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DNMT1 in Six2 progenitor cells is essential for transposable element silencing and kidney development

Project description:Cytosine methylation (5mC) plays a key role in maintaining progenitor cell self-renewal and differentiation. Here, we analyzed the role of 5mC in kidney development by genome-wide methylation and expression profiling and by systematic genetic targeting of DNA methyltransferases (Dnmt) and Tet eleven hydroxylases (Tet). In mice, nephrons differentiate from Six2+ progenitor cells, therefore we created animals with genetic deletion of Dnmt 1, 3a, 3b, Tet1, or Tet2 in the Six2+ population (Six2Cre/Dnmt1flox/flox, Six2Cre/Dnmt3aflox/flox, Six2Cre/Dnmt3bflox/flox, Six2Cre/Tet2flox/flox or Tet1-/-). Genome-wide methylation analysis indicated marked loss of methylation of transposable elements in Dnmt1 knock-out mice. RNA sequencing detected dedifferention of progenitor cells andtranscription of endogenous retroviral genes transcripts.

2019-03-15 | GSE110481 | GEO

DNMT1 in <i>Six2</i> Progenitor Cells Is Essential for Transposable Element Silencing and Kidney Development.

Project description:BackgroundCytosine methylation of regulatory regions, such as promoters and enhancers, plays a key role in regulating gene expression, however, its role in kidney development has not been analyzed.MethodsTo identify functionally important epigenome-modifying enzymes and genome regions where methylation modifications are functionally important for kidney development, we performed genome-wide methylation analysis, expression profiling, and systematic genetic targeting of DNA methyltransferases (Dnmt1, Dnmt3a, and Dnmt3b) and Ten-eleven translocation methylcytosine hydroxylases (Tet2) in nephron progenitor cells (Six2 Cre) in mice.ResultsGenome-wide methylome analysis indicated dynamic changes on promoters and enhancers during development. Six2 Cre Dnmt3a f/f, Six2 Cre Dnmt3b f/f, and Six2 Cre Tet2 f/f mice showed no significant structural or functional renal abnormalities. In contrast, Six2 Cre Dnmt1 f/f mice died within 24 hours of birth, from a severe kidney developmental defect. Genome-wide methylation analysis indicated a marked loss of methylation of transposable elements. RNA sequencing detected endogenous retroviral transcripts. Expression of intracellular viral sensing pathways (RIG-I), early embryonic, nonrenal lineage genes and increased cell death contributed to the phenotype development. In podocytes, loss of Dnmt1, Dnmt3a, Dnmt3b, or Tet2 did not lead to functional or structural differences at baseline or after toxic injury.ConclusionsGenome-wide cytosine methylation and gene expression profiling showed that by silencing embryonic, nonrenal lineage genes and transposable elements, DNMT1-mediated cytosine methylation is essential for kidney development.

| S-EPMC6442333 | biostudies-literature

Epigenomic conservation of transposable element silencing

Project description:Epigenomic conservation of transposable element silencing

| PRJNA379439 | ENA

Small RNA accumulation in Transposable Element-silent and Transposable Element-active epigenomes

Project description:Background: The small RNAs that Transposable Elements generate are vastly different when they are transcriptionally silenced compared to when they are transcriptionally activated. We performed the deep sequencing of small RNAs in a number of small RNA biogenesis mutants in both Transposable Element-silenced and Transposable Element-active epigenome backgrounds. Results: We found that Transposable Elements generate large amounts of 21-22nt siRNAs only when they are transcriptionally active. These 21-22nt siRNAs are incorporated into the AGO6 protein. Conclusion: Ago6 is the key protein that bridges the post-transcriptional degradation of Transposable Element mRNAs and the establishment of DNA methylation. Examination of flower bud small RNAs from wild type and 5 single or double mutant combinations, many of which have biological replicates. In addition, IP purification of the AGO6 protein (and mock no-antigen controls) followed by sequencing of the incorporated small RNAs. Replicate A for Col and ddm1 are submitted in GSE41755

2014-11-14 | E-GEOD-57191 | biostudies-arrayexpress

Small RNA accumulation in Transposable Element-silent and Transposable Element-active epigenomes

2014-11-14 | GSE57191 | GEO

Epigenomic conservation of transposable element silencing [RNA-seq]

Project description:Epigenomic conservation of transposable element silencing [RNA-seq]

| PRJNA379443 | ENA

Epigenomic conservation of transposable element silencing [ChIP-seq]

Project description:Epigenomic conservation of transposable element silencing [ChIP-seq]

| PRJNA379444 | ENA

Incorporation of transposable element small RNAs into the Arabidopsis AGO1 protein

Project description:Background: Transposable element 24 nucleotide small RNAs are not efficiently incorporated into the AGO1 protein, which is involved in endogenous RNAi and gene regulation through the microRNA and tasiRNA pathways. Results: The AGO1 protein incorporates large quantities of transposable element siRNAs when transposable elements are epigenetically activated and transcribed. The incorporation of transposable element siRNAs is at the expense of the most abundant microRNAs. These transposable element siRNAs can act as tasiRNAs, regulating genes that they have partial complementarity to. Conclusion: Transposable element small RNAs are more dynamic than previously thought. They can be incorporated into AGO1 and regulate genes. Three biological replicates of small RNA sequencing from two genotypes

2014-04-07 | E-GEOD-45990 | biostudies-arrayexpress

Incorporation of transposable element small RNAs into the Arabidopsis AGO1 protein

2014-04-07 | GSE45990 | GEO

Gene expression in Arabidopsis ddm1 mutants with high levels of Transposable Element activity

Project description:Background: Transposable elements are known to influence the regulation of some genes. We aimed to determine which genes show altered gene expression when transposable elements are epigenetically activated. Results: We find over 2000 genes with altered steady-state expression levels in ddm1 mutants. Some of these genes are influenced by neighboring transposable element fragments, while other genes are targeted by transposable element derived 21 nucleotide siRNAs. Conclusion: The regulation of the genic portion of the Arabidopsis genome is heavily influenced by the epigenetic regulation of transposable elements. The regulation of genes by transposable elements can occur through multiple mechanisms. Three biological replicates for two genotypes

2014-04-07 | E-GEOD-46050 | biostudies-arrayexpress

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