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Series GSE72469 Query DataSets for GSE72469
Status Public on Aug 28, 2015
Title Environmentally Induced Epigenetic Transgenerational Inheritance of Altered SRY Genomic Binding During Gonadal Sex Determination
Organism Rattus norvegicus
Experiment type Genome binding/occupancy profiling by genome tiling array
Summary A critical transcription factor required for mammalian male sex determination is SRY (sex determining region on the Y chromosome). The expression of SRY in precursor Sertoli cells is one of the initial events in testis development. The current study was designed to determine the impact of environmentally induced epigenetic transgenerational inheritance on SRY during gonadal sex determination in the male. The agricultural fungicide vinclozolin and vehicle control (DMSO) exposed gestating females (F0 generation) during gonadal sex determination promoted the transgenerational inheritance of differential DNA methylation in sperm of the F3 generation (great grand-offspring). The fetal gonads in F3 generation males were used to identify potential alterations in SRY binding sites in the developing Sertoli cells. Chromatin immunoprecipitation with an SRY antibody followed by genome-wide promoter tiling array (ChIP-Chip) was used to identify alterations in SRY binding. A total of 81 adjacent oligonucleotide sites and 173 single oligo SRY binding sites were identified to be altered transgenerationally in the Sertoli cell vinclozolin lineage F3 generation males. Observations demonstrate the majority of the previously identified normal SRY binding sites were not altered and the altered SRY binding sites were novel and new additional sites. The chromosomal locations, gene associations and potentially modified cellular pathways were investigated. In summary, environmentally induces epigenetic transgenerational inheritance of germline epimutations appears to alter the cellular differentiation and development of the precursor Sertoli cell SRY binding during gonadal sex determination that influence the developmental origins of adult onset testis disease.
Overall design The experimental design involved the intraperitoneal exposure of gestating female rats to vinclozolin or a vehicle control (dimethyl sulfoxide, DMSO) transiently from embryonic days E8-E14. Sister littermates were divided into control and vinclozolin treatment groups and mated to similar males to minimize the genetic variation between the control and vinclozolin lineages. Sufficient females were used so no inbreeding (sibling or cousin) occurred in any generation. The F1 generation was bred within the lineage to generate the F2 generation and these F2 generation bred to generate the F3 generation. The only exposure was the F0 generation female. The F3 generation control and vinclozolin lineage embryonic day 13 (E13) embryos were collected and the gonads micro-dissected and then sexed with an SRY PCR protocol. The male gonads were pooled from a minimum of three different litters and the pools used to collect DNA. Three different experiments were performed to collect 3 control and vinclozolin E13 F3 generation testis pools, each with different animals (n=25 gonads/pool). The chromatin DNA (not denatured) from each pool was fragmented and used in an SRY chromatin immunoprecipitation (ChIP) procedure for each pool separately. The control and vinclozolin SRY ChIP DNA were paired for a competitive hybridization on a genome-wide promoter tiling array (ChIP-Chip) assay. The hybridization data obtained was used to identify the SRY binding sites that were different in the F3 generation vinclozolin versus control lineage in E13 testis.
Contributor(s) Skinner MK, Bhandari R, Haque MM, Nilsson EE
Citation(s) 23555832
Submission date Aug 27, 2015
Last update date Oct 15, 2015
Contact name Michael K Skinner
Organization name WSU
Department SBS
Street address Abelson 507
City Pullman
State/province WA
ZIP/Postal code 99163
Country USA
Platforms (1)
GPL16994 NimbleGen Rat CpG Island Plus RefSeq Promoter 720k array [100718_RN34_CpG_Refseq_Prom_MeDIP]
Samples (3)
GSM1863006 E13-F3V1 / E13-F3C1
GSM1863007 E13-F3V2 / E13-F3C2
GSM1863008 E13-F3V3 / E13-F3C3
BioProject PRJNA294107

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE72469_RAW.tar 84.4 Mb (http)(custom) TAR (of XYS)
GSE72469_RegionsCombined_E13_SRY_ChIP.csv.gz 8.4 Kb (ftp)(http) CSV
Raw data provided as supplementary file
Processed data not applicable for this record

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