Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Comparison of the transcriptional profiles of male E13.5 wild type and L/H-Pgds-/- gonads

ABSTRACT: The goals of this study are to compare transcriptome profiling of L/H-Pgds-/- gonads to that of WT (RNA-seq) Methods: mRNA profiles of E13.5 wild-type (WT) and L- and H- prostaglandin D synthases (L/H-Pgds?/?) embryonic gonad were generated by deep sequencing, in triplicate, using Illumina HiSeq2000. qRT–PCR validation was performed using TaqMan and SYBR Green assays

ORGANISM(S): Mus musculus

SUBMITTER: Brigitte Boizet-Bonhoure

PROVIDER: E-GEOD-55744 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Prostaglandin D2 acts through the Dp2 receptor to influence male germ cell differentiation in the foetal mouse testis.

Moniot Brigitte B Ujjan Safdar S Champagne Julien J Hirai Hiroyuki H Aritake Kosuke K Nagata Kinya K Dubois Emeric E Nidelet Sabine S Nakamura Masataka M Urade Yoshihiro Y Poulat Francis F Boizet-Bonhoure Brigitte B

Development (Cambridge, England) 20140819 18

Through intercellular signalling, the somatic compartment of the foetal testis is able to program primordial germ cells to undergo spermatogenesis. Fibroblast growth factor 9 and several members of the transforming growth factor β superfamily are involved in this process in the foetal testis, counteracting the induction of meiosis by retinoic acid and activating germinal mitotic arrest. Here, using in vitro and in vivo approaches, we show that prostaglandin D2 (PGD2), which is produced through b ...[more]

PMID: 25142465

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Project description:Although technological advances now allow increased tumor profiling, a detailed understanding of the mechanisms leading to the development of different cancers remains elusive. Our approach towards understanding the molecular events that lead to cancer is to characterize changes in transcriptional regulatory networks between normal and tumor tissue. Because enhancer activity is thought to be critical in regulating cell fate decisions, we have focused our studies on distal regulatory elements and transcription factors that bind to these elements. Using DNA methylation data, we identified more than 25,000 enhancers that are differentially activated in breast, prostate, and kidney tumor tissues, as compared to normal tissues. We then developed an analytical approach called TENET (Tracing Enhancer Networks using Epigenetic Traits) that correlates DNA methylation levels at enhancers with gene expression to identify more than 800,000 genome-wide links from enhancers to genes and from genes to enhancers. We found more than 1,200 transcription factors to be involved in these tumor-specific enhancer networks. We further characterized several transcription factors linked to a large number of enhancers in each tumor type, including GATA3 in non-basal breast tumors, HOXC6 and DLX1 in prostate tumors, and ZNF395 in kidney tumors. We showed that HOXC6 and DLX1 are associated with different clusters of prostate tumor-specific enhancers and confer distinct transcriptomic changes upon knockdown in C42B prostate cancer cells. We also discovered de novo motifs enriched in enhancers linked to ZNF395 in kidney tumors. Our studies characterized tumor-specific enhancers and revealed key transcription factors involved in enhancer networks for specific tumor types and subgroups. Our findings, which include a large set of identified enhancers and transcription factors linked to those enhancers in breast, prostate, and kidney cancers, will facilitate understanding of enhancer networks and mechanisms leading to the development of these cancers. Examination of FAIRE and ChIP assays in prostate and breast epithelial cells. RNA-seq assays in C42B, prostate cancer cell line after knocking down of TFs (HOXC6, DLX1).

Dataset Information

Comparison of the transcriptional profiles of male E13.5 wild type and L/H-Pgds-/- gonads

Publications

Prostaglandin D2 acts through the Dp2 receptor to influence male germ cell differentiation in the foetal mouse testis.

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