Transcriptional profiling of JEG3 cells with HLA-G ablation via deletion of Enhancer L
Transcriptomics Dataset
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General Information
AccessionGSE79779
TitleTranscriptional profiling of JEG3 cells with HLA-G ablation via deletion of Enhancer L
DescriptionHLA-G is a nonclassical HLA molecule expressed specifically in the placenta. While it is known to play a central role in maternal immune tolerance during pregnancy, the mechanism underlying its tissue-specific expression remains poorly understood. To elucidate this mechanism, we used a Massively Parallel Reporter Assay (MPRA) to systematically interrogate the HLA-G locus. This uncovered Enhancer L, a novel cis-regulatory element with enhancer activity 12kb upstream of HLA-G. To verify enhancer function and specificity for HLA-G in culture, we deleted Enhancer L in JEG3 cells and performed RNA sequencing and differential expression analysis. Upon Enhancer L knockout, we observe complete ablation of HLA-G and minimal dysregulation of other genes within 2Mb, suggesting that HLA-G is the only direct cis target of Enhancer L. DNase-seq and Chromatin Conformation Capture (3C) confirm that Enhancer L is a cell type-specific enhancer that loops into the HLA-G promoter. MPRA-based saturation mutagenesis of Enhancer L identifies motifs for transcription factors of the CEBP and GATA families which are essential for placentation. These factors associate with Enhancer L and regulate HLA-G expression. Our findings identify long-range chromatin looping mediated by core trophoblast transcription factors as a novel mechanism controlling tissue-specific HLA-G expression at the maternal-fetal interface.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE79779
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Dataset Accession
ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
Canned Analyses generated with the dataset
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Interactive heatmap visualization of RNA-seq dataset GSE79779
ARCHS4, Clustergrammer
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
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