Endogenous retroviruses (ERVs) have accumulated in vertebrate genomes and contribute to the complexity of gene regulation. KAP1 represses ERVs during development by its recruitment to their repetitive sequences through KRAB-zinc finger proteins (KZNFs), but little is known about the regulation of ERVs in differentiated cells. We observed that KAP1 repression of HERVK14C was conserved in differentiated human cells and performed KAP1 knockout to obtain an overview of KAP1 function. Our results show that KAP1 represses ERVs (including HERV-T and HERV-S) and ZNFs, both of which overlap with KAP1 binding sites and H3K9me3 in multiple cell types. Furthermore, this pathway is functionally conserved in primary peripheral blood mononuclear cells. Cytosine methylation that acts on KAP1-regulated loci is necessary to prevent an interferon response, and KAP1-depletion leads to activation of some interferon-stimulated genes. Finally, loss of KAP1 leads to a decrease in H3K9me3 enrichment at ERVs and ZNFs and an RNA-sensing response mediated through MAVS signaling. These data indicate that the KAP1-KZNF pathway contributes to genome stability and innate immune control in differentiated human cells. Overall design: Dissection of which transposons and genes KAP1 regulates in differentiated human cells
KAP1 regulates endogenous retroviruses in adult human cells and contributes to innate immune control.
Cell line, Subject
View SamplesCancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small cell lung cancer (NSCLC), we compared RNAseq data of 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the CTdatabase, 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase. Cluster analysis revealed that CTA expression is histology-dependent and concurrent expression is common. Immunohistochemistry confirmed tissue specific protein expression of selected genes. Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from the Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer, was not confirmed, neither in our RNAseq-cohort nor in an independent meta-analysis of 1117 NSCLC cases. Overall design: Fresh frozen tumor tissue from 199 patients diagnosed with NSCLC and surgically treated 2006-2010 at the Uppsala University Hospital, Uppsala, Sweden and 19 paired normal lung tissues. Clinical data were retrieved from the regional lung cancer registry. Several of the new CTAs are poorly characterized Sample characteristics values represent; pTNM: decided by Hans Brunnström, pathologist in Lund Spring 2013 Stage according to pTNM: 1=1a 2=1b 3=2a 4=2b 5=3a 6=3b 7=IV Histology diagnosis spring 2013 HB: 1=squamous cell cancer 2=AC unspecified 3=Large cell/ NOS Surgery date: the date when sample arrived at Patologen UAS Age: age when surgery was performed Vital date: day of death or latest contact Dead: 0=no 1= yes Smoking history : 1=current 2=ex >1year 3=never WHO performance status: Performance status 0-4 Please note that the L608T_2122, L771T_1 data columns (in the processed data files) are associated with L608T and L771T samples, respectively.
Multispectral imaging for quantitative and compartment-specific immune infiltrates reveals distinct immune profiles that classify lung cancer patients.
No sample metadata fields
View SamplesABSTRACT: Background: Though central to our understanding of how roots perform their vital function of scavenging water and solutes from the soil, no direct genetic evidence currently exists to support the foundational model that suberin acts to form a chemical barrier limiting the extracellular, or apoplastic, transport of water and solutes in plant roots.
Root suberin forms an extracellular barrier that affects water relations and mineral nutrition in Arabidopsis.
Specimen part
View SamplesTo investigate genes possibly regulated by TTF-1 in small cell lung cancer cell lines, we compared gene expression profiles of NCI-H209 and Lu139 cell lines electroporated with control and TTF-1 siRNAs.
An integrative transcriptome analysis reveals a functional role for thyroid transcription factor-1 in small cell lung cancer.
Cell line
View SamplesMolecular profiling of 159 lung cancers of different histological subtypes. A primary objective is to identify gene expression differences between histological subtypes. Sample overlap exist with GSE60644
Gene Expression Profiling of Large Cell Lung Cancer Links Transcriptional Phenotypes to the New Histological WHO 2015 Classification.
Sex, Age
View SamplesTo identify gene expression profiles in those periodontitis-associated fibroblasts (PAFs) versus normal gingival fibroblasts to determine their molecular repertoire, and exploit it for therapeutic intervention.
Fibroblast VEGF-receptor 1 expression as molecular target in periodontitis.
Specimen part, Subject
View SamplesASCL1 is a master transcription factor for neuroendocrine differentiation. RNA-sequencing analysis on VMRC-LCD cells following ASCL1 knockdown revealed a subset of genes possibly regulated by ASCL1. Overall design: VMRC-LCD cells were transfected with siRNAs for ASCL1, and RNA-sequencing was performed using Illumina HiSeq.
An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1-Positive Lung Adenocarcinomas.
Cell line, Subject
View SamplesTranscriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis
Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.
Specimen part
View SamplesTranscriptome analyses of normal gingival fibroblasts after knockdown of DLX5 and RUNX2 long forms.
Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.
Specimen part
View SamplesTo investigate the roles of TAZ in lung cancer cell proliferation, we compared the expression profiles of A549 and H441 lung adenocarcinoma cell lines transfected with control siRNA and siTAZ.
An integrative analysis of the tumorigenic role of TAZ in human non-small cell lung cancer.
Specimen part, Cell line
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