Epigenomic remodeling of the PAX8 cistrome in high grade serous ovarian cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Kevin Elias
PROVIDER: E-GEOD-83101 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:We report mapping of the PAX8 cistrome in three high grade serous ovarian cancer cell lines (KURAMOCHI, OVSAHO, and JHOS4) compared to three benign immortalized fallopian tube cell lines (FT33, FT194, and FT246). We identified a highly conserved PAX8 binding pattern common across benign fallopian tube cell lines that was distinct from the unique PAX8 binding patterns seen in each cancer cell line. Comparison of benign and malignant Mullerian cell lines with and without PAX8 knockdown. For each cell line, three distinct siRNAs targeting PAX8 plus a pool of all three siRNAs were examined and compared to both a non-transfected control as well as a control transfected with a non-targeting siRNA.
2016-08-08 | E-GEOD-83100 | biostudies-arrayexpress
Project description:We report mapping of the PAX8 cistrome in three high grade serous ovarian cancer cell lines (KURAMOCHI, OVSAHO, and JHOS4) compared to three benign immortalized fallopian tube cell lines (FT33, FT194, and FT246). We identified a highly conserved PAX8 binding pattern common across benign fallopian tube cell lines that was distinct from the unique PAX8 binding patterns seen in each cancer cell line. Comparison of benign and malignant Mullerian cell lines.
2016-08-08 | E-GEOD-79893 | biostudies-arrayexpress
Project description:The goals of this study were to identify LIN28 downstream gene targets in breast cancer cells. We use a subclone of the MCF-7 breast cancer cell line, MCF-7M as our model system. Methods: mRNA profiles from MCF-7M breast cancer cells treated with siRNA against non-targeting control (NT), LIN28, hnRNP A1, LIN28 and hnRNPA1 (LIN28A1) for 72 hrs were generated by deep sequencing, in duplicate, using Illumina HiSeq 2000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays Results: Using an optimized data analysis workflow, we mapped over 200 million sequence reads per sample to the human genome (build h19). Each of the four groups had two biological replicates. We developed a custom method to identify alternative splicing events and identified 111 genes with significant (FDR<0.05) differential splicing for LIN28 depleted cells compared to non-targeting siRNA control, as well as 249 and 182 genes for hnRNP A1 and LIN28A1 respectively. RNA-seq data were validated with by qRT–PCR analysis of a subset of genes. Conclusions: Results reveal that LIN28 regulates alternative splicing and steady state mRNA expression of genes implicated in aspects of breast cancer biology. Notably, cells lacking LIN28 undergo significant isoform switching of the ENAH gene, resulting in a decrease in the expression of ENAH exon 11a isoform. Expression of ENAH isoform 11a has been shown to be elevated in breast cancers that express HER2. mRNA profiles of MCF-7M cells treated with siRNA for NT control, LIN28, hnRNP A1, and LIN28 plus hnRNP A1 (A1) (LIN28A1) were generated by deep sequencing, in duplicate, using Illumina HiSeq 2000
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Project description:The epithelium lining the epididymis in the male reproductive tract maintains a luminal environment that promotes sperm cell maturation. This process is dependent on the coordinated expression of many genes that encode proteins with a role in epithelial transport. We previously generated genome-wide maps of open chromatin in primary human fetal epididymis epithelial cells to identify potential regulatory elements controlling coordinated gene expression in the epididymis epithelium. Subsequent in silico analysis identified transcription factor binding sites (TFBS) that were over-represented in the HEE open chromatin, include the motif for paired box 2 (PAX2). PAX2 is a critical transcriptional regulator of urogenital tract development, which is well studied in the kidney but is unexplored in the epididymis. Due to the limited lifespan of primary HEE cells in culture we investigated the role of PAX2 in an immortalized HEE cell line (REP). First, REP cells were evaluated by DNase-seq and their open chromatin map overlapped that of primary HEE cells at ~ 65% of sites. Moreover, the PAX2-binding motif was again identified as an overrepresented TFBS within intergenic open chromatin, though on fewer chromosomes than in the primary HEE cells. To identify PAX2-target genes in REP cells, RNA-seq analysis was performed after siRNA-mediated depletion of PAX2 in comparison to a non-targeting siRNA. In response to PAX2-represssion, 3142 transcripts were differentially expressed (1334 up-regulated and 1808 down-regulated). Novel PAX2 targets included multiple genes encoding proteins with a predicted function in the epididymis epithelium. mRNA profile of control and PAX2 knockdown REP cells
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Project description:In order to define the transcriptional network functionally regulated by Pax8 as well as infer its direct targets, we performed RNAi to knock-down Pax8 gene in FRTL-5 thyroid cells. Expression data from three independent silencing experiments were analyzed by microarray technology unraveling 2815 genes differentially expressed between silenced cells and controls. Of these, 1421 genes were down-regulated and 1394 genes were up-regulated 72hrs after Pax8 silencing. The results obtained suggest that Pax8 regulates numerous pathways, some of which involved in the regulation of cell cycle, thyroid cancer and apoptosis, thus confirming that Pax8 is a master regulatory gene. Rat differentiated thyroid cells from FRTL-5 line were transfected with siGENOME Pax8 siRNA (siPax8, experimental) or siGENOME Non-Targeting siRNA (ntPax8, controls). The trascriptome from three siPax8 biological replicates, 72 hours after transfection, was compared to the trascriptome from 3 control ntPax8 biological replicates. Microarray analysis was performed at gene-level using the AffymetrixGeneChip Rat Gene 1.0 ST array
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