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...

Descripción completa

Detalles Bibliográficos
Autores principales: SAITO, Takeshi, HARA, Satoshi, TAMANO, Moe, ASAHARA, Hiroshi, TAKADA, Shuji
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