Cargando…
Deletion of conserved sequences in IG-DMR at Dlk1-Gtl2 locus suggests their involvement in expression of paternally expressed genes in mice
Expression regulation of the Dlk1-Dio3 imprinted domain by the intergenic differentially methylated region (IG-DMR) is essential for normal embryonic development in mammals. In this study, we investigated conserved IG-DMR genomic sequences in eutherians to elucidate their role in genomic imprinting...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Society for Reproduction and Development
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320436/ https://www.ncbi.nlm.nih.gov/pubmed/27904015 http://dx.doi.org/10.1262/jrd.2016-135 |
_version_ | 1782509535255068672 |
---|---|
author | SAITO, Takeshi HARA, Satoshi TAMANO, Moe ASAHARA, Hiroshi TAKADA, Shuji |
author_facet | SAITO, Takeshi HARA, Satoshi TAMANO, Moe ASAHARA, Hiroshi TAKADA, Shuji |
author_sort | SAITO, Takeshi |
collection | PubMed |
description | Expression regulation of the Dlk1-Dio3 imprinted domain by the intergenic differentially methylated region (IG-DMR) is essential for normal embryonic development in mammals. In this study, we investigated conserved IG-DMR genomic sequences in eutherians to elucidate their role in genomic imprinting of the Dlk1-Dio3 domain. Using a comparative genomics approach, we identified three highly conserved sequences in IG-DMR. To elucidate the functions of these sequences in vivo, we generated mutant mice lacking each of the identified highly conserved sequences using the CRISPR/Cas9 system. Although mutant mice did not exhibit the gross phenotype, deletions of the conserved sequences altered the expression levels of paternally expressed imprinted genes in the mutant embryos without skewing imprinting status. These results suggest that the conserved sequences in IG-DMR are involved in the expression regulation of some of the imprinted genes in the Dlk1-Dio3 domain. |
format | Online Article Text |
id | pubmed-5320436 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Society for Reproduction and Development |
record_format | MEDLINE/PubMed |
spelling | pubmed-53204362017-02-27 Deletion of conserved sequences in IG-DMR at Dlk1-Gtl2 locus suggests their involvement in expression of paternally expressed genes in mice SAITO, Takeshi HARA, Satoshi TAMANO, Moe ASAHARA, Hiroshi TAKADA, Shuji J Reprod Dev Original Article Expression regulation of the Dlk1-Dio3 imprinted domain by the intergenic differentially methylated region (IG-DMR) is essential for normal embryonic development in mammals. In this study, we investigated conserved IG-DMR genomic sequences in eutherians to elucidate their role in genomic imprinting of the Dlk1-Dio3 domain. Using a comparative genomics approach, we identified three highly conserved sequences in IG-DMR. To elucidate the functions of these sequences in vivo, we generated mutant mice lacking each of the identified highly conserved sequences using the CRISPR/Cas9 system. Although mutant mice did not exhibit the gross phenotype, deletions of the conserved sequences altered the expression levels of paternally expressed imprinted genes in the mutant embryos without skewing imprinting status. These results suggest that the conserved sequences in IG-DMR are involved in the expression regulation of some of the imprinted genes in the Dlk1-Dio3 domain. The Society for Reproduction and Development 2016-12-01 2017-02 /pmc/articles/PMC5320436/ /pubmed/27904015 http://dx.doi.org/10.1262/jrd.2016-135 Text en ©2017 Society for Reproduction and Development This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: http://creativecommons.org/licenses/by-nc-nd/4.0/) |
spellingShingle | Original Article SAITO, Takeshi HARA, Satoshi TAMANO, Moe ASAHARA, Hiroshi TAKADA, Shuji Deletion of conserved sequences in IG-DMR at Dlk1-Gtl2 locus suggests their involvement in expression of paternally expressed genes in mice |
title | Deletion of conserved sequences in IG-DMR at Dlk1-Gtl2 locus suggests their involvement in expression of
paternally expressed genes in mice |
title_full | Deletion of conserved sequences in IG-DMR at Dlk1-Gtl2 locus suggests their involvement in expression of
paternally expressed genes in mice |
title_fullStr | Deletion of conserved sequences in IG-DMR at Dlk1-Gtl2 locus suggests their involvement in expression of
paternally expressed genes in mice |
title_full_unstemmed | Deletion of conserved sequences in IG-DMR at Dlk1-Gtl2 locus suggests their involvement in expression of
paternally expressed genes in mice |
title_short | Deletion of conserved sequences in IG-DMR at Dlk1-Gtl2 locus suggests their involvement in expression of
paternally expressed genes in mice |
title_sort | deletion of conserved sequences in ig-dmr at dlk1-gtl2 locus suggests their involvement in expression of
paternally expressed genes in mice |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320436/ https://www.ncbi.nlm.nih.gov/pubmed/27904015 http://dx.doi.org/10.1262/jrd.2016-135 |
work_keys_str_mv | AT saitotakeshi deletionofconservedsequencesinigdmratdlk1gtl2locussuggeststheirinvolvementinexpressionofpaternallyexpressedgenesinmice AT harasatoshi deletionofconservedsequencesinigdmratdlk1gtl2locussuggeststheirinvolvementinexpressionofpaternallyexpressedgenesinmice AT tamanomoe deletionofconservedsequencesinigdmratdlk1gtl2locussuggeststheirinvolvementinexpressionofpaternallyexpressedgenesinmice AT asaharahiroshi deletionofconservedsequencesinigdmratdlk1gtl2locussuggeststheirinvolvementinexpressionofpaternallyexpressedgenesinmice AT takadashuji deletionofconservedsequencesinigdmratdlk1gtl2locussuggeststheirinvolvementinexpressionofpaternallyexpressedgenesinmice |