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Microarray-based global mapping of integration sites of retrotransposon, intracisternal A-particle, in mouse genome

ABSTRACT: Mammalian genomes have evolutionary harbored numerous mobile elements, a part of which are still active and evoke genomic instability. Their movement and positional diversity occasionally result in phenotypic changes and variation by causing altered expression and disruption of neighboring genes in the host genome. Here, we describe a novel microarray-based method by which dispersed genomic locations of a type of retrotransposons in mammalian genome can be identified at a time. By this method, we mapped the DNA elements for a mouse retrotransposon, intracisternal A-particle (IAP), within genomes of C3H/He and C57BL/6J inbred mouse strains; consequently we detected hundreds of probable IAP cDNA-integrating genomic regions. Among 147 putative insertions located nearby the promoter regions, 91 were considered to be present discriminatively in the genome either of C3H/He or C57BL/6J mice, suggesting the existence of considerable strain differences. In addition, by comparing genomic DNAs from a radiation-induced myeloid leukemia and its reference normal tissue, we detected 3 genomic regions around which an IAP element was integrated. These results demonstrate for the first time the successful genome-wide survey of a type of retrotransposon in mammalian genome. Keywords: retrotransposon mapping

ORGANISM(S): Mus musculus

PROVIDER: GSE9572 | GEO | 2008/05/03

SECONDARY ACCESSION(S): PRJNA103399

REPOSITORIES: GEO

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Microarray-based global mapping of integration sites of retrotransposon, intracisternal A-particle, in mouse genome

Project description:Mammalian genomes have evolutionary harbored numerous mobile elements, a part of which are still active and evoke genomic instability. Their movement and positional diversity occasionally result in phenotypic changes and variation by causing altered expression and disruption of neighboring genes in the host genome. Here, we describe a novel microarray-based method by which dispersed genomic locations of a type of retrotransposons in mammalian genome can be identified at a time. By this method, we mapped the DNA elements for a mouse retrotransposon, intracisternal A-particle (IAP), within genomes of C3H/He and C57BL/6J inbred mouse strains; consequently we detected hundreds of probable IAP cDNA-integrating genomic regions. Among 147 putative insertions located nearby the promoter regions, 91 were considered to be present discriminatively in the genome either of C3H/He or C57BL/6J mice, suggesting the existence of considerable strain differences. In addition, by comparing genomic DNAs from a radiation-induced myeloid leukemia and its reference normal tissue, we detected 3 genomic regions around which an IAP element was integrated. These results demonstrate for the first time the successful genome-wide survey of a type of retrotransposon in mammalian genome. Keywords: retrotransposon mapping Genomic DNA fragments containing sequences that flank a mouse retrotransposon are purified and hybridized to the microarray. Experiments are comparisions between signal intensities obtained from Cy3-labeled purified DNA fragments (test) and Cy5-labeled whole genomic DNA fragments (reference).

2008-05-03 | E-GEOD-9572 | biostudies-arrayexpress

Whole brain gene expression in X-monosomic and normal female mice

Project description:Whole brain gene expression was examined in the following strains of mice: 1. P0 maternal monosomic 39,Xm females, C57BL/6J x C3H/Paf 2. P0 paternal monosomic 39, Xp females, In(X)/C3H x C57BL/6J 3. P0 normal 40,XX females, In(X)/C3H x C57BL/6J 4. P0 normal 40,XX females, C57BL/6J x C3H/Paf Keywords = imprinting Keywords = mammalian genetics Keywords = X-linked Keywords = brain Keywords: other

2005-05-02 | GSE1606 | GEO

Transcription profiling of mouse whole brain gene expression in X-monosomic and normal female mice

Project description:Whole brain gene expression was examined in the following strains of mice: 1. P0 maternal monosomic 39,Xm females, C57BL/6J x C3H/Paf; 2. P0 paternal monosomic 39, Xp females, In(X)/C3H x C57BL/6J; 3. P0 normal 40,XX females, In(X)/C3H x C57BL/6J; 4. P0 normal 40,XX females, C57BL/6J x C3H/Paf

2007-10-11 | E-GEOD-1606 | biostudies-arrayexpress

Comparative phenotypic assessment of cardiac pathology, physiology, and gene expression in C3H/HeJ, C57BL/6J, and B6C3F1/J mice

Project description:Human cardiomyopathies often lead to heart failure, a major cause of morbidity and mortality in industrialized nations. Described here is a phenotypic characterization of cardiac function and genome-wide expression from C3H/HeJ, C57BL/6J, and B6C3F1/J male mice. Histopathologic analysis identified a low-grade background cardiomyopathy (murine progressive cardiomyopathy) in eight of nine male C3H/HeJ mice (age nine to ten weeks), but not in male C57BL/6J and in only of ten male B6C3F1/J mice. The C3H/HeJ mouse had an increased heart rate and a shorter RR interval compared to the B6C3F1/J and C57BL/6J mice. Cardiac genomic studies indicated the B6C3F1/J mice exhibited an intermediate gene expression phenotype relative to the 2 parental strains. Disease-centric enrichment analysis indicated a number of cardiomyopathy-associated genes were induced in B6C3F1/J and C3H/HeJ mice, including Myh7, My14, and Lmna and also indicated differential expression of genes associated with metabolic (e.g., Pdk2) and hypoxic stress (e.g. Hif1a). A novel coexpression and integrated pathway network analysis indicated Prkaa2, Pdk2, Rhoj, and Sgcb are likely to play a central role in the pathophysiology of murine progressive cardiomyopathy in C3H/HeJ mice. Our studies indicate that genetically determined baseline differences in cardiac phenotype have the potential to influence the results of cardiotoxicity studies.

2019-11-15 | GSE140418 | GEO

Protein O-GlcNAcylation Silences Methylated Promoters in Mammalian Genomes

Project description:Methylated mammalian promoters are transcriptionally silenced even in the presence of all the factors required for their expression. Repression requires the assembly of a methylation-dependent silencing complex that contains the TRIM28 (also known as KAP1 and TIF1β) protein. An internally controlled interaction screen identified O-linked β-N-acetylglucosamine transferase (O-GlcNAc transferase or OGT) as a protein that was complexed with TRIM28 in wild type em-bryonic stem cells but not in Dnmt1-/- cells that had severely demethylated genomes. In the ab-sence of DNA methylation, multiple proteins associated with TRIM28 failed to undergo modifica-tion by N-Acetylglucosamine (GlcNAc). Mass spectrometry identified several of these proteins as known mediators of transcriptional silencing. The most active transposon in the mouse ge-nome is the IAP LTR retrotransposon, which have been previously shown to be repressed by DNA methylation. A Bacteroides O-GlcNAc hydrolase was fused to a catalytically inactive Cas9 and targeted to methylated IAP retrotransposon promoter sequences via IAP-specific guide RNAs; fulminating reactivation of IAP transcription was induced. These data revealed that Glc-NAcylation is directly involved in the transcriptional repression of methylated promoters.

2020-05-29 | GSE93539 | GEO

Mouse brain region gene expression (430 2.0 Array)

Project description:Gene expression patterns were determined from five brain regions (bed nucleus of the stria terminalis, hippocampus, hypothalamus, periaqueductal gray, and pituitary gland) in six mouse strains (129S6/SvEvTac, A/J, C57BL/6J, C3H/HeJ, DBA/2J, and FVB/NJ). At least two replicate samples per brain region/strain were analyzed using Affymetrix Mouse Genome 430 2.0 arrays. Keywords: mouse strain and brain region comparison

2007-03-05 | GSE4734 | GEO

Inter-strain epigenomic profiling reveals a candidate IAP master copy in C3H mice

Project 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 insertionally polymorphic IAPs have accumulated faster in C3H/HeJ mice relative to other 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 for H3K4me3 (a mark of active promoters) and, among those tested, all are unmethylated in C3H 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.

2020-06-10 | GSE152208 | GEO

Transcription profiling of mouse brain regions (bed nucleus of the stria terminalis, hippocampus, hypothalamus, periaqueductal gray, and pituitary gland) in six mouse strains (129S6/SvEvTac, A/J, C57BL/6J, C3H/HeJ, DBA/2J, and FVB/NJ)

2009-09-16 | E-GEOD-4734 | biostudies-arrayexpress

strain dependent pulmonary bleomycin response

Project description:right lung gene expression of C57BL/6J, A/J and C3H/HeJ mice following bleomcyin exposure Keywords: other

2005-12-29 | GSE2640 | GEO

Sex differences in the ventral tegmental area and nucleus accumbens proteome at baseline and following nicotine exposure

Project description:Sex differences in behaviors relevant to nicotine addiction have been observed in rodent models and human subjects. Behavioral, imaging and epidemiological studies also suggest underlying sex differences in mesolimbic dopamine signaling pathways. In this study we evaluated the proteome in the ventral tegmental area (VTA) and nucleus accumbens (NAc) shell in male and female mice. Experimental groups included two mouse strains (C3H/HeJ and C57BL/6J) at baseline, a sub-chronic, rewarding regimen of nicotine in C3H/HeJ mice, and chronic nicotine administration and withdrawal in C57BL/6J mice. Isobaric labeling with a TMT 10-plex system, sample fractionation, and tandem mass spectrometry were used to quantify changes in protein abundance. Similar or greater numbers of differentially regulated proteins were found between sexes at baseline in C3H/HeJ or C57BL/6J mice than within sexes following their respective regimen of nicotine administration. Despite differences by sex, strain, and nicotine exposure parameters, glial fibrillary acidic protein (GFAP) and dopamine and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32, Ppp1r1b) were repeatedly identified as significantly altered proteins, especially in the VTA. Further, network analyses showed sex- and nicotine-dependent regulation of a number of signaling pathways, including dopaminergic signaling. Sub-chronic nicotine exposure in female mice increased proteins related to dopaminergic signaling in the NAc shell but decreased them in the VTA, whereas the opposite pattern was observed in male mice. In contrast, dopaminergic signaling pathways were similarly upregulated in both male and female VTA after chronic nicotine and withdrawal. Overall, this study identifies significant sex differences in the proteome of the mesolimbic system, at baseline and after nicotine reward or withdrawal, which may help explain differential trajectories and susceptibility to nicotine addiction in males and females.

2021-06-28 | PXD023859 | Pride

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