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Series GSE118827 Query DataSets for GSE118827
Status Public on Dec 10, 2020
Title Sodium arsenite exposure inhibits histone acetyltransferase p300 for attenuating H3K27ac at enhancers in mouse embryonic fibroblast cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Both epidemiological investigations and animal studies have linked arsenic-contaminated water to cancers, in- cluding skin, liver and lung cancers. Besides genotoxicity, arsenic exposure-related pathogenesis of disease is widely considered through epigenetic mechanisms; however, the underlying mechanism remains to be deter- mined. Herein we explore the initial epigenetic changes via acute sodium arsenite (As) exposures of mouse em- bryonic fibroblast (MEF) cells and histone H3K79 methyltransferase Dot1L knockout (Dot1Lāˆ’ā  /āˆ’) MEF cells. Our RNA-seq and Western blot data demonstrated that, in both cell lines, acute As exposure abolished histone acetyl- transferase p300 at the RNA level and subsequent protein level. Consequently, p300-specific main target histone H3K27ac, a marker separating active from poised enhancers, decreased dramatically as validated by both West- ern blot and ChIP-qPCR/seq analyses. Concomitantly, H3K4me1 as another well-known marker for enhancers also showed significant decreases, suggesting an underappreciated crosstalk between H3K4me1 and H3K27ac involved in As exposure. Significantly, As exposure-reduced H3K27ac and H3K4me1 inhibited the expression of genes including EP300 itself and Kruppel Like Factor 4(Klf4) that both are tumor suppressor genes. Collectively, our investigations identified p300 as an internal bridging factor within cells to sense external environmental As exposure to alter chromatin, thereby changing gene transcription for disease pathogenesis.
 
Overall design RNA-seq were performed for the control and low dose As treated MEF cell and Dot1L mutant to explore the whole genome wide transcriptional response to the low dose As. In addition, we also investigated changes in histone mark H3K27ac occupancy at the MEF and As treated MEF cells to see the histone change at the enhancer or promoter reigions of the differentially expressed genes.
 
Contributor(s) Li Y, Wang Z
Citation(s) 30130555
Submission date Aug 21, 2018
Last update date Feb 03, 2022
Contact name Yanqiang Li
Organization name Boston Children's Hospital
Department Cardiology Department
Lab Kaifu Chen Lab
Street address 300 Longwood Ave.
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
 
Platforms (1)
GPL21273 HiSeq X Ten (Mus musculus)
Samples (6)
GSM3348297 MEF Control RNA-seq
GSM3348298 MEF low As treated RNA-seq
GSM3348299 Dot1L Control RNA-seq
Relations
BioProject PRJNA486912
SRA SRP158481

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE118827_MEF_Dot1L_As_treated.RNAseq.rpkm.txt.gz 712.7 Kb (ftp)(http) TXT
GSE118827_RAW.tar 217.5 Mb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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