University of Surrey

Test tubes in the lab Research in the ATI Dance Research

Expression at the Imprinted Dlk1-Gtl2 Locus Is Regulated by Proneural Genes in the Developing Telencephalon

Seibt, Julie, Armant, Olivier, Le Digarcher, Anne, Castro, Diogo, Ramesh, Vidya, Journot, Laurent, Guillemot, Francois, Vanderhaeghen, Pierre and Bouschet, Tristan (2012) Expression at the Imprinted Dlk1-Gtl2 Locus Is Regulated by Proneural Genes in the Developing Telencephalon PLoS ONE, 7 (11), e48675.

[img]
Preview
Text
__homes.surrey.ac.uk_home_.System_Desktop_Seibt (2012) PLoS ONE.pdf - Version of Record

Download (4MB) | Preview

Abstract

Imprinting is an epigenetic mechanism that restrains the expression of about 100 genes to one allele depending on its parental origin. Several imprinted genes are implicated in neurodevelopmental brain disorders, such as autism, Angelman, and Prader-Willi syndromes. However, how expression of these imprinted genes is regulated during neural development is poorly understood. Here, using single and double KO animals for the transcription factors Neurogenin2 (Ngn2) and Achaetescute homolog 1 (Ascl1), we found that the expression of a specific subset of imprinted genes is controlled by these proneural genes. Using in situ hybridization and quantitative PCR, we determined that five imprinted transcripts situated at the Dlk1-Gtl2 locus (Dlk1, Gtl2, Mirg, Rian, Rtl1) are upregulated in the dorsal telencephalon of Ngn2 KO mice. This suggests that Ngn2 influences the expression of the entire Dlk1-Gtl2 locus, independently of the parental origin of the transcripts. Interestingly 14 other imprinted genes situated at other imprinted loci were not affected by the loss of Ngn2. Finally, using Ngn2/Ascl1 double KO mice, we show that the upregulation of genes at the Dlk1-Gtl2 locus in Ngn2 KO animals requires a functional copy of Ascl1. Our data suggest a complex interplay between proneural genes in the developing forebrain that control the level of expression at the imprinted Dlk1-Gtl2 locus (but not of other imprinted genes). This raises the possibility that the transcripts of this selective locus participate in the biological effects of proneural genes in the developing telencephalon.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Seibt, Juliej.seibt@surrey.ac.uk
Armant, Olivier
Le Digarcher, Anne
Castro, Diogo
Ramesh, Vidya
Journot, Laurent
Guillemot, Francois
Vanderhaeghen, Pierre
Bouschet, Tristan
Date : 6 November 2012
DOI : 10.1371/journal.pone.0048675
Copyright Disclaimer : �2012 Seibt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Depositing User : Melanie Hughes
Date Deposited : 28 Aug 2018 12:04
Last Modified : 28 Aug 2018 12:04
URI: http://epubs.surrey.ac.uk/id/eprint/849122

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800