Localizing transcriptional regulatory elements at the mouse Dlk1 locus.

Much effort has focused recently on determining the mechanisms that control the allele-specific expression of genes subject to genomic imprinting, yet imprinting regulation is only one aspect of configuring appropriate expression of these genes. Imprinting control mechanisms must interact with those...

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Autores principales: Eric D Rogers, Jenniffer R Ramalie, Erin N McMurray, Jennifer V Schmidt
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Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/c9e203ad5dcd4c34abe872e7d0096cc6
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spelling oai:doaj.org-article:c9e203ad5dcd4c34abe872e7d0096cc62021-11-18T07:19:03ZLocalizing transcriptional regulatory elements at the mouse Dlk1 locus.1932-620310.1371/journal.pone.0036483https://doaj.org/article/c9e203ad5dcd4c34abe872e7d0096cc62012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22606264/?tool=EBIhttps://doaj.org/toc/1932-6203Much effort has focused recently on determining the mechanisms that control the allele-specific expression of genes subject to genomic imprinting, yet imprinting regulation is only one aspect of configuring appropriate expression of these genes. Imprinting control mechanisms must interact with those regulating the tissue-specific expression pattern of each imprinted gene in a cluster. Proper expression of the imprinted Delta-like 1 (Dlk1)-Maternally expressed gene 3 (Meg3) gene pair is required for normal fetal development in mammals, yet the mechanisms that control tissue-specific expression of these genes are unknown. We have used a combination of in vivo and in vitro expression assays to localize cis-regulatory elements that may regulate Dlk1 expression in the mouse embryo. A bacterial artificial chromosome transgene encompassing the Dlk1 gene and 77 kb of flanking sequence conferred expression in most endogenous Dlk1-expressing tissues. In combination with previous transgenic data, these experiments localize the majority of Dlk1 cis-regulatory elements to a 41 kb region upstream of the gene. Cross-species sequence conservation was used to further define potential regulatory elements, several of which functioned as enhancers in a luciferase expression assay. Two of these elements were able to drive expression of a lacZ reporter transgene in Dlk1-expressing tissues in the mouse embryo. The sequence proximal to Dlk1 therefore contains at least two discrete regions that may regulate tissue-specificity of Dlk1 expression.Eric D RogersJenniffer R RamalieErin N McMurrayJennifer V SchmidtPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e36483 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Eric D Rogers
Jenniffer R Ramalie
Erin N McMurray
Jennifer V Schmidt
Localizing transcriptional regulatory elements at the mouse Dlk1 locus.
description Much effort has focused recently on determining the mechanisms that control the allele-specific expression of genes subject to genomic imprinting, yet imprinting regulation is only one aspect of configuring appropriate expression of these genes. Imprinting control mechanisms must interact with those regulating the tissue-specific expression pattern of each imprinted gene in a cluster. Proper expression of the imprinted Delta-like 1 (Dlk1)-Maternally expressed gene 3 (Meg3) gene pair is required for normal fetal development in mammals, yet the mechanisms that control tissue-specific expression of these genes are unknown. We have used a combination of in vivo and in vitro expression assays to localize cis-regulatory elements that may regulate Dlk1 expression in the mouse embryo. A bacterial artificial chromosome transgene encompassing the Dlk1 gene and 77 kb of flanking sequence conferred expression in most endogenous Dlk1-expressing tissues. In combination with previous transgenic data, these experiments localize the majority of Dlk1 cis-regulatory elements to a 41 kb region upstream of the gene. Cross-species sequence conservation was used to further define potential regulatory elements, several of which functioned as enhancers in a luciferase expression assay. Two of these elements were able to drive expression of a lacZ reporter transgene in Dlk1-expressing tissues in the mouse embryo. The sequence proximal to Dlk1 therefore contains at least two discrete regions that may regulate tissue-specificity of Dlk1 expression.
format article
author Eric D Rogers
Jenniffer R Ramalie
Erin N McMurray
Jennifer V Schmidt
author_facet Eric D Rogers
Jenniffer R Ramalie
Erin N McMurray
Jennifer V Schmidt
author_sort Eric D Rogers
title Localizing transcriptional regulatory elements at the mouse Dlk1 locus.
title_short Localizing transcriptional regulatory elements at the mouse Dlk1 locus.
title_full Localizing transcriptional regulatory elements at the mouse Dlk1 locus.
title_fullStr Localizing transcriptional regulatory elements at the mouse Dlk1 locus.
title_full_unstemmed Localizing transcriptional regulatory elements at the mouse Dlk1 locus.
title_sort localizing transcriptional regulatory elements at the mouse dlk1 locus.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/c9e203ad5dcd4c34abe872e7d0096cc6
work_keys_str_mv AT ericdrogers localizingtranscriptionalregulatoryelementsatthemousedlk1locus
AT jennifferrramalie localizingtranscriptionalregulatoryelementsatthemousedlk1locus
AT erinnmcmurray localizingtranscriptionalregulatoryelementsatthemousedlk1locus
AT jennifervschmidt localizingtranscriptionalregulatoryelementsatthemousedlk1locus
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