Transcriptomics

Dataset Information

72

Microarray analysis of HCT116 cells with and without a 1.4kb deletion


ABSTRACT: One of the strongest associated type 2 diabetes (T2D) loci reported to date resides within the TCF7L2 gene. Previous studies point to the T allele of rs7903146 in intron 3 as the causal variant at this locus. To aid in the identification of the actual gene(s) under the influence of this variant, we first generated a CRISPR/Cas9 mediated 1.4kb deletion of the genomic region harboring rs7903146 in the HCT116 cell line followed by global gene expression analysis. HCT116 cells with or without a CRISPR/Cas9 mediated1.4kb deletion of the genomic region harboring the SNP rs7903146 were analyzed for expression, with 3 replicates per condition (DEL vs WT). We observed 99 genes with significant differential expression (FDR cut-off=10%) and an effect size of at least two-fold. We then carried out high-throughput chromosome conformation capture assays in the HCT116 and NCM460 cell lines and in colon tissue (see experiment E-MTAB-4845) in order to ascertain which of these perturbed genes’ promoters made consistent physical contact with the genomic region harboring the variant. This revealed just one gene, ACSL5, which resides in the same topologically associating domain as TCF7L2.

ORGANISM(S): Homo sapiens  

SUBMITTER: Struan F.A. Grant   Elisabetta Manduchi   Qianghua Xia  

PROVIDER: E-MTAB-4839 | ArrayExpress | 2016-08-16

REPOSITORIES: ArrayExpress

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Publications

The type 2 diabetes presumed causal variant within TCF7L2 resides in an element that controls the expression of ACSL5.

Xia Qianghua Q   Chesi Alessandra A   Manduchi Elisabetta E   Johnston Brian T BT   Lu Sumei S   Leonard Michelle E ME   Parlin Ursula W UW   Rappaport Eric F EF   Huang Peng P   Wells Andrew D AD   Blobel Gerd A GA   Johnson Matthew E ME   Grant Struan F A SFA  

Diabetologia 20160818 11


One of the most strongly associated type 2 diabetes loci reported to date resides within the TCF7L2 gene. Previous studies point to the T allele of rs7903146 in intron 3 as the causal variant at this locus. We aimed to identify the actual gene(s) under the influence of this variant.Using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease, we generated a 1.4 kb deletion of the genomic region harbouring rs7903146 in the HCT116 cell line, followe  ...[more]

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