Inter-Strain Epigenomic Profiling Reveals a Candidate IAP Master Copy in C3H Mice
department or school: Medicine, Faculty of
department or school: Non UBC
department or school: Medical Genetics, Department of
data provider: DSpace
identifier citation: Viruses 12 (7): 783 (2020)
creator: Rebollo, Rita
creator: Galvão-Ferrarini, Mariana
creator: Gagnier, Liane
creator: Zhang, Ying
creator: Ferraj, Ardian
creator: Beck, Christine R.
creator: Lorincz, Matthew C.
creator: Mager, Dixie L.
issued: 2020-07-30T21:47:22Z
issued: 2020-07-21
description: Insertions of endogenous retroviruses cause a significant fraction of mutations in inbred mice but not all strains are equally susceptible. Notably, most new Intracisternal A particle (IAP) ERV mutagenic insertions have occurred in C3H mice. We show here that strain-specific insertional polymorphic IAPs accumulate faster in C3H/HeJ mice, relative to other sequenced strains, and that IAP transcript levels are higher in C3H/HeJ embryonic stem (ES) cells compared to other ES cells. To investigate the mechanism for high IAP activity in C3H mice, we identified 61 IAP copies in C3H/HeJ ES cells enriched with H3K4me3 (a mark of active promoters) and, among those tested, all are unmethylated in C3H/HeJ ES cells. Notably, 13 of the 61 are specific to C3H/HeJ and are members of the non-autonomous 1Δ1 IAP subfamily that is responsible for nearly all new insertions in C3H. One copy is full length with intact open reading frames and hence potentially capable of providing proteins in trans to other 1Δ1 elements. This potential “master copy” is present in other strains, including 129, but its 5’ long terminal repeat (LTR) is methylated in 129 ES cells. Thus, the unusual IAP activity in C3H may be due to reduced epigenetic repression coupled with the presence of a master copy.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/75345
note: virusesArticleInter-Strain Epigenomic Profiling Reveals aCandidate IAP Master Copy in C3H MiceRita Rebollo 1,2,* , Mariana Galvão-Ferrarini 2 , Liane Gagnier 1, Ying Zhang 1, Ardian Ferraj 3,Christine R. Beck 3,4, Matthew C. Lorincz 5 and Dixie L. Mager 1,5,*1 Terry Fox Laboratory, British Columbia Cancer, Vancouver, BC V5Z1L3, Canada;liane.gagnier@bccdc.ca (L.G.); ying.zhang.phd@gmail.com (Y.Z.)2 University of Lyon, INSA-Lyon, INRA, BF2i, UMR0203, F-69621 Villeurbanne, France;mariana.galvao-ferrarini@insa-lyon.fr3 Department of Genetics and Genome Sciences, University of Connecticut Health Center,Farmington, CT 06030, USA; Ardian.Ferraj@jax.org (A.F.); Christine.Beck@jax.org (C.R.B.)4 The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA5 Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T1Z3, Canada;mlorincz@mail.ubc.ca* Correspondence: rita.rebollo@inrae.fr (R.R.); dmager@bccrc.ca (D.L.M.)Received: 11 June 2020; Accepted: 13 July 2020; Published: 21 July 2020Abstract: Insertions of endogenous retroviruses cause a significant fraction of mutations in inbredmice but not all strains are equally susceptible. Notably, most new Intracisternal A particle (IAP)ERV mutagenic insertions have occurred in C3H mice. We show here that strain-specific insertionalpolymorphic IAPs accumulate faster in C3H/HeJ mice, relative to other sequenced strains, and thatIAP transcript levels are higher in C3H/HeJ embryonic stem (ES) cells compared to other ES cells.To investigate the mechanism for high IAP activity in C3H mice, we identified 61 IAP copies inC3H/HeJ ES cells enriched with H3K4me3 (a mark of active promoters) and, among those tested,all are unmethylated in C3H/HeJ ES cells. Notably, 13 of the 61 are specific to C3H/HeJ and aremembers of the non-autonomous 1∆1 IAP subfamily that is responsible for nearly all new insertionsin C3H. One copy is full length with intact open reading frames and hence potentially capable ofproviding prot…
has type: Article
is shown at: 10.14288/1.0392612
language: eng
peer review status: Reviewed
provider: Vancouver : University of British Columbia Library
publisher: Multidisciplinary Digital Publishing Institute
publisher DOI: 10.3390/v12070783
rights: CC BY 4.0
rights URI: https://creativecommons.org/licenses/by/4.0/
scholar level: Faculty
scholar level: Researcher
subject: transposable elements
subject: endogenous retrovirus
subject: mouse
subject: C3H
subject: IAP
subject: epigenetics
type: Text
identifier URI: http://hdl.handle.net/2429/75345