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| Status |
Public on Mar 08, 2017 |
| Title |
Genome-wide profiling of gene expression/splicing patterns in iAs-transformed cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Chronic low dose inorganic arsenic (iAs) exposure leads to changes in gene expression and epithelial-to-mesenchymal transformation. During this transformation, cells adopt a fibroblast-like phenotype accompanied by profound gene expression changes. While many mechanisms have been implicated in this transformation, studies that focus on the role of epigenetic alterations in this process are just emerging. DNA methylation controls gene expression in physiologic and pathologic states. Several studies show alterations in DNA methylation patterns in iAs-mediated pathogenesis, but these studies focused on single genes. We present a comprehensive genome-wide DNA methylation analysis using methyl-sequencing to measure changes between normal and iAs-transformed cells. Additionally, these differential methylation changes correlated positively with changes in gene expression and alternative splicing. Interestingly, most of these differentially methylated genes function in cell adhesion and communication pathways. To gain insight into how genomic DNA methylation patterns are regulated iAs-mediated carcinogenesis, we show that iAs probably targets CTCF binding at the promoter of DNA methyltransferases, regulating their expression. These findings reveal how transcription factor binding regulates DNA methyltransferase to reprogram the methylome in response to an environmental toxin.
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| Overall design |
To examine the global impact of iAs on gene expression and splicing patterns, RNA was extracted from 2 replicates of normal (NT) BEAS-2B cells and 2 replicates of inorganic arsenic-transformed (iAs-T) BEAS-2B cells and analyzed using Affymetrix Human Transcriptome 2.0 arrays.
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| Contributor(s) |
Rea M, Eckstein M, Eleazer R, Smith C, Rouchka EC, Fondufe-Mittendorf Y |
| Citation(s) |
28150704 |
| Submission date |
Dec 02, 2016 |
| Last update date |
Oct 29, 2018 |
| Contact name |
Eric Christian Rouchka |
| E-mail(s) |
eric.rouchka@louisville.edu
|
| Organization name |
University of Louisville
|
| Department |
Biochemistry and Molecular Genetics
|
| Lab |
KY INBRE Bioinformatics Core
|
| Street address |
522 East Gray Street
|
| City |
Louisville |
| State/province |
Kentucky |
| ZIP/Postal code |
40292 |
| Country |
USA |
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| Platforms (2) |
| GPL17585 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [probe set (exon) version] |
| GPL17586 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version] |
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| Samples (8)
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| GSM2413391 |
Normal (NT) Replicate 1 [gene level] |
| GSM2413392 |
Normal (NT) Replicate 2 [gene level] |
| GSM2413393 |
Inorganic arsenic-transformed (iAs-T) Replicate 1 [gene level] |
| GSM2413394 |
Inorganic arsenic-transformed (iAs-T) Replicate 2 [gene level] |
| GSM2413395 |
Normal (NT) Replicate 1 [splice level] |
| GSM2413396 |
Normal (NT) Replicate 2 [splice level] |
| GSM2413397 |
Inorganic arsenic-transformed (iAs-T) Replicate 1 [splice level] |
| GSM2413398 |
Inorganic arsenic-transformed (iAs-T) Replicate 2 [splice level] |
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| Relations |
| BioProject |
PRJNA356040 |
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