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Genome‐wide combinatorial transcriptional regulatory dynamics during early onset of liver regeneration and chronic alcohol intake
Author(s) -
PATRA BISWANATH,
Kuttippurathu Lakshmi,
COOK DAN,
HOEK JAN B,
Vadigepalli Rajanikanth
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1161.5
Subject(s) - histone , dna methylation , biology , epigenetics , transcriptome , liver regeneration , regeneration (biology) , gene , methylation , gene expression profiling , cell cycle , genetics , gene expression
The objective of this study is to identify genome‐scale transcriptional regulatory network dynamics affected by chronic alcohol intake during the early phase of liver regeneration. Rats were fed liquid diet containing 36% of total calories derived from ethanol for 5 weeks, and controls were pair‐fed an isocaloric liquid diet. A 70% partial hepatectomy (PHx) was performed. Genome‐wide binding targets for NF‐kB, C/EBP‐beta, and STAT3 were detected either by Roche NimbleGen ChIP‐chip or ABI SOLiD sequencing approach. Our findings indicate significant differences in the binding profiles of all the three regulators in chronic ethanol compared to isocaloric controls, at baseline as well as in response to PHx. Pathway analysis revealed that potential target genes specific to the chronic ethanol group participate in key processes such as mitochondria processing, DNA methylation, cell death, proteolysis, histone modification, lipid biosynthetic process, and regulation of cell cycle etc. Our results revealed combinatorial binding dynamics of multiple TFs from ChIP‐seq and DNA binding motif. Our results provide a first system‐wide view of the regulatory network dynamics in liver regeneration as it is affected by alcohol, and implicate combinatorial regulatory modules as participating in the adverse liver regeneration response. Research Support: NIH R01 AA018873 , K05 AA017261 , and T32 AA007463.