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Maternal Low Protein Diet Induces ATF3 but not ASNS Expression in Liver of Female Offspring Through Amino Acid Response (AAR) Pathway
Author(s) -
Zhou Dan,
Pan Yuan Xiang
Publication year - 2010
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.24.1_supplement.331.6
Subject(s) - atf3 , chromatin immunoprecipitation , atf4 , histone , gene silencing , chromatin , biology , histone h3 , microbiology and biotechnology , transcription factor , promoter , gene expression , gene , genetics
Objective To investigate the impact of maternal low protein on programming of AAR pathway. Method Sprague‐Dawley rats were fed a control (18% protein) or low protein diet (LP, 9% protein) during gestation. Liver from female offspring was collected at 38 days of age to analyze expression and histone modification of genes in AAR pathway. Result expression of ATF3 in LP group increased significantly. ATF4 and p‐eIF2alpha, key upstream factors in AAR pathway, were up‐regulated as well. Chromatin immunoprecipitation assay confirmed that Pol II and ATF4 binding was increased at the ATF3 promoter while there was a decrease of ATF3 and C/EBPbeta binding. On the other hand, promoter of the downstream gene ASNS showed a different profile. Acetylated histone H4, a marker for an open chromatin was increased at the ASNS promoter, along with an increased binding of ATF4, ATF3 and C/EBPbeta. However, tri‐methyl histone H3 at lysine 9, a marker for chromatin silencing, was increased in LP group, possibly leading to no change in Pol II binding and therefore no change in ASNS gene expression level. Conclusion Maternal low protein diet programs AAR pathway in liver of female offspring. This programming occurs at upstream of AAR pathway, mainly affecting gene expression of transcription factors, including ATF4 and ATF3. Furthermore this may prime the downstream target genes such as ASNS to respond to low protein environment later. Grant Funding Source: USDA