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SOX15 governs a transcriptional program in human esophageal stratified epithelium and in a subset of esophageal adenocarcinomas

ABSTRACT: We identified spatially restricted transcription factors and found SOX15 expression confined to stratified esophageal epithelium, with attenuation in Barrett's esophagus. SOX15 binds esophagus-specific loci and its loss in human esophageal cells affected esophagus-specific transcripts

ORGANISM(S): Homo sapiens

PROVIDER: GSE62909 | GEO | 2015/11/09

SECONDARY ACCESSION(S): PRJNA266111

REPOSITORIES: GEO

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SOX15 governs a transcriptional program in human esophageal stratified epithelium and in a subset of esophageal adenocarcinomas

Project description:We identified spatially restricted transcription factors and found SOX15 expression confined to stratified esophageal epithelium, with attenuation in Barrett's esophagus. SOX15 binds esophagus-specific loci and its loss in human esophageal cells affected esophagus-specific transcripts [RNA-Seq] Total RNA isolated from CPA control cells and CPA cells following SOX15 depletion, samples were prepared for sequencing using the TruSeq RNA Sample Preparation Kit (Illumina) according to the manufacturer's instructions. 75 base pair single-end reads were sequenced on an Illumina NextSeq 500 instrument. The data include 2 independent biological replicates per genotype. [ChIP-Seq] Examine SOX15-chromatin binding in CPA cells.

2015-11-09 | E-GEOD-62909 | biostudies-arrayexpress

SOX15 governs transcription in human stratified epithelia and a subset of esophageal adenocarcinomas.

Project description:Background & aimsIntestinal metaplasia (Barrett's esophagus, BE) is the principal risk factor for esophageal adenocarcinoma (EAC). Study of the basis for BE has centered on intestinal factors, but loss of esophageal identity likely also reflects absence of key squamous-cell factors. As few determinants of stratified epithelial cell-specific gene expression are characterized, it is important to identify the necessary transcription factors.MethodsWe tested regional expression of mRNAs for all putative DNA-binding proteins in the mouse digestive tract and verified esophagus-specific factors in human tissues and cell lines. Integration of diverse data defined a human squamous esophagus-specific transcriptome. We used chromatin immunoprecipitation (ChIP-seq) to locate transcription factor binding sites, computational approaches to profile transcripts in cancer datasets, and immunohistochemistry to reveal protein expression.ResultsThe transcription factor SOX15 is restricted to esophageal and other murine and human stratified epithelia. SOX15 mRNA levels are attenuated in BE and its depletion in human esophageal cells reduced esophageal transcripts significantly and specifically. SOX15 binding is highly enriched near esophagus-expressed genes, indicating direct transcriptional control. SOX15 and hundreds of genes co-expressed in squamous cells are reactivated in up to 30% of EAC specimens. Genes normally confined to the esophagus or intestine appear in different cells within the same malignant glands.ConclusionsThese data identify a novel transcriptional regulator of stratified epithelial cells and a subtype of EAC with bi-lineage gene expression. Broad activation of squamous-cell genes may shed light on whether EACs arise in the native stratified epithelium or in ectopic columnar cells.

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