ZFP57 regulation of transposable elements and gene expression within and beyond imprinted domains
Abstract Background KRAB zinc finger proteins (KZFPs) represent one of the largest families of DNA-binding proteins in vertebrate genomes and appear to have evolved to silence transposable elements (TEs) including endogenous retroviruses through sequence-specific targeting of repressive chromatin st...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-08-01
|
| Series: | Epigenetics & Chromatin |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13072-019-0295-4 |
| _version_ | 1818609660133900288 |
|---|---|
| author | Hui Shi Ruslan Strogantsev Nozomi Takahashi Anastasiya Kazachenka Matthew C. Lorincz Myriam Hemberger Anne C. Ferguson-Smith |
| author_facet | Hui Shi Ruslan Strogantsev Nozomi Takahashi Anastasiya Kazachenka Matthew C. Lorincz Myriam Hemberger Anne C. Ferguson-Smith |
| author_sort | Hui Shi |
| collection | DOAJ |
| description | Abstract Background KRAB zinc finger proteins (KZFPs) represent one of the largest families of DNA-binding proteins in vertebrate genomes and appear to have evolved to silence transposable elements (TEs) including endogenous retroviruses through sequence-specific targeting of repressive chromatin states. ZFP57 is required to maintain the post-fertilization DNA methylation memory of parental origin at genomic imprints. Here we conduct RNA-seq and ChIP-seq analyses in normal and ZFP57 mutant mouse ES cells to understand the relative importance of ZFP57 at imprints, unique and repetitive regions of the genome. Results Over 80% of ZFP57 targets are TEs, however, ZFP57 is not essential for their repression. The remaining targets lie within unique imprinted and non-imprinted sequences. Though the loss of ZFP57 influences imprinted genes as expected, the majority of unique gene targets lose H3K9me3 with little effect on DNA methylation and very few exhibit alterations in expression. Comparison of ZFP57 mutants with DNA methyltransferase-deleted ES cells (TKO) identifies a remarkably similar pattern of H3K9me3 loss across the genome. These data define regions where H3K9me3 is secondary to DNA methylation and we propose that ZFP57 is the principal if not sole methylation-sensitive KZFP in mouse ES cells. Finally, we examine dynamics of DNA and H3K9 methylation during pre-implantation development and show that sites bound by ZFP57 in ES cells maintain DNA methylation and H3K9me3 at imprints and at non-imprinted regions on the maternally inherited chromosome throughout preimplantation development. Conclusion Our analyses suggest the evolution of a rare DNA methylation-sensitive KZFP that is not essential for repeat silencing, but whose primary function is to maintain DNA methylation and repressive histone marks at germline-derived imprinting control regions. |
| first_indexed | 2024-12-16T15:02:04Z |
| format | Article |
| id | doaj.art-3be2fb7bcee5404f99a63cecfba56468 |
| institution | Directory Open Access Journal |
| issn | 1756-8935 |
| language | English |
| last_indexed | 2024-12-16T15:02:04Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj.art-3be2fb7bcee5404f99a63cecfba564682022-12-21T22:27:15ZengBMCEpigenetics & Chromatin1756-89352019-08-0112111310.1186/s13072-019-0295-4ZFP57 regulation of transposable elements and gene expression within and beyond imprinted domainsHui Shi0Ruslan Strogantsev1Nozomi Takahashi2Anastasiya Kazachenka3Matthew C. Lorincz4Myriam Hemberger5Anne C. Ferguson-Smith6Department of Genetics, University of CambridgeDepartment of Genetics, University of CambridgeDepartment of Genetics, University of CambridgeDepartment of Genetics, University of CambridgeDepartment of Medical Genetics, University of British ColumbiaBabraham Institute, Epigenetics ISPDepartment of Genetics, University of CambridgeAbstract Background KRAB zinc finger proteins (KZFPs) represent one of the largest families of DNA-binding proteins in vertebrate genomes and appear to have evolved to silence transposable elements (TEs) including endogenous retroviruses through sequence-specific targeting of repressive chromatin states. ZFP57 is required to maintain the post-fertilization DNA methylation memory of parental origin at genomic imprints. Here we conduct RNA-seq and ChIP-seq analyses in normal and ZFP57 mutant mouse ES cells to understand the relative importance of ZFP57 at imprints, unique and repetitive regions of the genome. Results Over 80% of ZFP57 targets are TEs, however, ZFP57 is not essential for their repression. The remaining targets lie within unique imprinted and non-imprinted sequences. Though the loss of ZFP57 influences imprinted genes as expected, the majority of unique gene targets lose H3K9me3 with little effect on DNA methylation and very few exhibit alterations in expression. Comparison of ZFP57 mutants with DNA methyltransferase-deleted ES cells (TKO) identifies a remarkably similar pattern of H3K9me3 loss across the genome. These data define regions where H3K9me3 is secondary to DNA methylation and we propose that ZFP57 is the principal if not sole methylation-sensitive KZFP in mouse ES cells. Finally, we examine dynamics of DNA and H3K9 methylation during pre-implantation development and show that sites bound by ZFP57 in ES cells maintain DNA methylation and H3K9me3 at imprints and at non-imprinted regions on the maternally inherited chromosome throughout preimplantation development. Conclusion Our analyses suggest the evolution of a rare DNA methylation-sensitive KZFP that is not essential for repeat silencing, but whose primary function is to maintain DNA methylation and repressive histone marks at germline-derived imprinting control regions.http://link.springer.com/article/10.1186/s13072-019-0295-4DNA methylationKZFPsZFP57Transposable elementsEmbryonic stem cells |
| spellingShingle | Hui Shi Ruslan Strogantsev Nozomi Takahashi Anastasiya Kazachenka Matthew C. Lorincz Myriam Hemberger Anne C. Ferguson-Smith ZFP57 regulation of transposable elements and gene expression within and beyond imprinted domains Epigenetics & Chromatin DNA methylation KZFPs ZFP57 Transposable elements Embryonic stem cells |
| title | ZFP57 regulation of transposable elements and gene expression within and beyond imprinted domains |
| title_full | ZFP57 regulation of transposable elements and gene expression within and beyond imprinted domains |
| title_fullStr | ZFP57 regulation of transposable elements and gene expression within and beyond imprinted domains |
| title_full_unstemmed | ZFP57 regulation of transposable elements and gene expression within and beyond imprinted domains |
| title_short | ZFP57 regulation of transposable elements and gene expression within and beyond imprinted domains |
| title_sort | zfp57 regulation of transposable elements and gene expression within and beyond imprinted domains |
| topic | DNA methylation KZFPs ZFP57 Transposable elements Embryonic stem cells |
| url | http://link.springer.com/article/10.1186/s13072-019-0295-4 |
| work_keys_str_mv | AT huishi zfp57regulationoftransposableelementsandgeneexpressionwithinandbeyondimprinteddomains AT ruslanstrogantsev zfp57regulationoftransposableelementsandgeneexpressionwithinandbeyondimprinteddomains AT nozomitakahashi zfp57regulationoftransposableelementsandgeneexpressionwithinandbeyondimprinteddomains AT anastasiyakazachenka zfp57regulationoftransposableelementsandgeneexpressionwithinandbeyondimprinteddomains AT matthewclorincz zfp57regulationoftransposableelementsandgeneexpressionwithinandbeyondimprinteddomains AT myriamhemberger zfp57regulationoftransposableelementsandgeneexpressionwithinandbeyondimprinteddomains AT annecfergusonsmith zfp57regulationoftransposableelementsandgeneexpressionwithinandbeyondimprinteddomains |