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Title: Novel Comparative Pattern Count Analysis Reveals a Chronic Ethanol Induced Dynamic Shift In NF-κB Genome-wide Promoter Binding During Liver Regeneration      
keywords:
Epigenomics
ID:
PRJNA299606
description:
We analyzed the effect of chronic alcohol intake on the genome-wide binding activity of NF-κB during the initial response phase following partial hepatectomy. We analyzed the data in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found several ethanol-specific NF-κB binding target promoters in the chronic adapted state.. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns between ethanol and isocaloric pair-fed control groups. We found that NF-κB bound genes govern negative regulation of cell growth and inflammatory response immediately following hepatectomy. We, integrated the ChIP-chip results with a time series gene expression data set to identify the NF-κB promoter binding targets that showed differential gene expression changes at the baseline-adapted condition as well as after PHx. We identified a set of differential patterns of NF-κB binding that were specific to the ethanol and pair-fed control groups. We found the regulatory pathways and co-incident transcription factor binding motifs corresponding some of the key comparative-binding patterns. Overall design: Adult (8-10 week old) Sprague-Dawley rats were fed a liquid diet containing 36% of total calories derived from ethanol for 5 weeks, with the pair-fed calorie-matched littermate controls receiving liquid diets in which ethanol calories were replaced by carbohydrate . When their weight reached 275-350 g, they were anesthetized and subjected to 70% partial hepatecomy by surgical removal of medial and left lateral lobes as per standard procedure. The medial and left lateral lobes were flash frozen using liquid nitrogen-cooled aluminum clamps to serve as within-animal, 0 hour controls. At 1 hou and 6 hours post-PHx, rats (three biological replicates per time) were again anesthetized and the remnant liver tissue was excised and flash-frozen as before. Following excision of the remaining liver mass, rats were sacrificed by cervical dislocation. Liver tissue from 0h, 1h and 6h post-PHx was subjected to chromatin immunoprecipitation. Immunoprecipitated samples (ChIP) from 0h, 1h, and 6h post-PHx were used to identifiy genome-wide NF-κB binding sites using microarrays (ChIP-chip).
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA299606
authentication:
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authorization:
none
name:
Rattus norvegicus
ncbiID:
ncbitax:10116
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information