 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Sep 19, 2019 |
| Title |
Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues [Bisulfite-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
|
| Summary |
Background: Genomic imprinting is an epigenetic phenomenon that allows a subset of genes to be expressed mono-allelically based on parent-of-origin, and is typically regulated by differential DNA methylation inherited from gametes. Imprinting is pervasive in murine extra-embryonic lineages and, uniquely, the imprinting of several genes has been found to be conferred non-canonically through maternally-inherited repressive histone modification H3K27me3. However, the underlying regulatory mechanisms of non-canonical imprinting in post-implantation development remain unexplored.
Results: We identify imprinted regions in post-implantation epiblast and extra-embryonic ectoderm (ExE) by assaying allelic histone modifications (H3K4me3, H3K36me3, H3K27me3), gene expression and DNA methylation in reciprocal C57BL/6 and CAST hybrid embryos. We distinguish loci with DNA methylation- dependent (canonical) and independent (non-canonical) imprinting by assaying hybrid embryos with ablated maternally-inherited DNA methylation. We find that non-canonical imprints are localized to endogenous retrovirus-K (ERVK) long terminal repeats (LTRs), which act as imprinted promoters specifically in extra-embryonic lineages. Transcribed ERVK LTRs are CpG-rich and located in close proximity to gene promoters, and imprinting status is determined by their epigenetic patterning in the oocyte. Finally, we show that oocyte-derived H3K27me3 associates with non-canonical imprints is not maintained beyond pre-implantation development, and is replaced by secondary imprinted DNA methylation on the maternal allele in post-implantation ExE, while being completely silenced by bi-allelic DNA methylation in epiblast.
Conclusions: This study reveals distinct epigenetic mechanisms regulating non-canonical imprinted gene expression between embryonic and extra-embryonic development, and identifies an integral role for ERVK LTR repetitive elements.
|
| |
|
| Overall design |
To evaluate the allelic regulation of histone modifications in the embryo, we assayed H3K4me3, H3K36me3 and H3K27me3 using ultra low-input ChIP-seq (Hanna et al. 2018) and post-bisulfite adaptor tagging (PBAT) in reciprocal hybrid (C57BL6/Babr x CAST/Ei) embryonic day (E) 6.5 epiblast and extra-embryonic ectoderm (ExE). We additionally profiled these epigenetic marks in E6.5 embryos derived from females with a double conditional knockout for Dnmt3a and Dnmt3b in oocytes (matDKO), driven by Zp3-cre. Consequently, these matDKO embryos will inherit no maternal DNA methylation, but are able to sufficiently establish DNA methylation post-fertilisation. Allelic gene expression was evaluated in E7.5 epiblast and ExE of all hybrid crosses.
|
| |
|
| Contributor(s) |
Hanna C, Krueger F, Andrews S, Dean W, Kelsey G |
| Citation(s) |
31665063, 36690623 |
| |
| Submission date |
Dec 20, 2018 |
| Last update date |
Feb 07, 2023 |
| Contact name |
Felix Krueger |
| E-mail(s) |
fkrueger@altoslabs.com
|
| Organization name |
Altos Labs
|
| Department |
Bioinformatics
|
| Street address |
Granta Park
|
| City |
Cambridge |
| ZIP/Postal code |
CB21 6GP |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (23)
|
|
| This SubSeries is part of SuperSeries: |
| GSE124216 |
Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues |
|
| Relations |
| BioProject |
PRJNA510998 |
| SRA |
SRP174096 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE124213_Bisulfite_100_CpG_windows_Epi_ExE_DNAme.txt.gz |
20.9 Mb |
(ftp)(http) |
TXT |
| GSE124213_Bisulphite_100CpGwindows_E7.5Epi_ExE_DNAme.txt.gz |
21.0 Mb |
(ftp)(http) |
TXT |
| GSE124213_Bisulphite_100CpGwindows_E7.5Epi_ExE_allelicDNAme.txt.gz |
25.1 Mb |
(ftp)(http) |
TXT |
| GSE124213_RAW.tar |
311.1 Mb |
(http)(custom) |
TAR (of COV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...