|
| Status |
Public on Jun 18, 2021 |
| Title |
Dnmt1 has global de novo methylation activity and is specifically targeted to transposable elements |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Other
|
| Summary |
DNA methylation plays a critical role in development, particularly in silencing transposable elements. Conserved across mammals, the methylation landscape is dependent on the combined activities of the canonical maintenance enzyme Dnmt1 and the de novo Dnmts 3a and 3b. Here we demonstrate that Dnmt1 displays clear de novo activity in vitro and in vivo and is specifically directed to IAP retrotransposons. We provide an indepth characterization using whole genome bisulfite sequencing and long-read Nanopore sequencing in genetically engineered methylation depleted embryonic stem cells. Further using additional knockout and MassSpec experiments we show that Dnmt1’s de novo methylation activity is dependent on Uhrf1 and its genomic targeting linked to Trim28 and H3K9 trimethylation. Our data suggest that Dnmt1 is essential for adding and maintaining DNA methylation especially at IAPs and that this mechanism may be of physiological relevance for retrotransposon repression during certain phases of development.
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| |
|
| Overall design |
Analysis of Dnmt1 de novo activity in DNA methylation depleted ES cells and during development.
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| Contributor(s) |
Haggerty C, Kretzmer H, Riemenschneider C, Sampath Kumar A, Weigert R, Bailly N, Mattei A, Gießelmann P, Brändl B, Galonska C, Timmermann B, Meierhofer D, Meissner A |
| Citation(s) |
34140676 |
|
https://doi.org/10.1038/s41594-021-00603-8
|
| |
| Submission date |
Sep 23, 2020 |
| Last update date |
Jul 28, 2021 |
| Contact name |
Helene Kretzmer |
| E-mail(s) |
kretzmer@molgen.mpg.de
|
| Organization name |
Max Planck Institute for Molecular Genetics
|
| Department |
Genome Regulation
|
| Lab |
Meissner Lab
|
| Street address |
Ihnestraße 63
|
| City |
Berlin |
| ZIP/Postal code |
14195 |
| Country |
Germany |
| |
|
| Platforms (4)
|
| GPL16417 |
Illumina MiSeq (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (90)
|
|
| Relations |
| BioProject |
PRJNA665263 |
| SRA |
SRP285138 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE158460_BS_hairpin.csv.gz |
887 b |
(ftp)(http) |
CSV |
| GSE158460_BS_hairpin.xlsx |
13.4 Kb |
(ftp)(http) |
XLSX |
| GSE158460_DKOzero_H3K9me3.broadPeak.bed.gz |
2.2 Mb |
(ftp)(http) |
BED |
| GSE158460_DKOzero_H3K9me3_FE.bw |
1.2 Gb |
(ftp)(http) |
BW |
| GSE158460_DKOzero_Trim28.broadPeak.bed.gz |
1.4 Mb |
(ftp)(http) |
BED |
| GSE158460_DKOzero_Trim28_FE.bw |
136.0 Mb |
(ftp)(http) |
BW |
| GSE158460_DKOzero_Uhrf1.broadPeak.bed.gz |
727.9 Kb |
(ftp)(http) |
BED |
| GSE158460_DKOzero_Uhrf1_FE.bw |
1.3 Gb |
(ftp)(http) |
BW |
| GSE158460_RAW.tar |
6.8 Gb |
(http)(custom) |
TAR (of BED, BW) |
| GSE158460_TKOlike_H3K9me3.broadPeak.bed.gz |
2.4 Mb |
(ftp)(http) |
BED |
| GSE158460_TKOlike_H3K9me3_FE.bw |
715.2 Mb |
(ftp)(http) |
BW |
| GSE158460_TKOlike_Trim28.broadPeak.bed.gz |
1.3 Mb |
(ftp)(http) |
BED |
| GSE158460_TKOlike_Trim28_FE.bw |
770.8 Mb |
(ftp)(http) |
BW |
| GSE158460_TKOlike_Uhrf1.broadPeak.bed.gz |
969.7 Kb |
(ftp)(http) |
BED |
| GSE158460_TKOlike_Uhrf1_FE.bw |
1.3 Gb |
(ftp)(http) |
BW |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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