Ontogenic expression of hepatic Ahr mRNA is associated with histone H3K4 di-methylation during mouse liver development.
The aryl hydrocarbon receptor (Ahr) is a xenobiotic sensor that regulates the expression of a battery of drug-metabolizing genes. However, Ahr is also important for normal liver development. The purpose of the present study was to examine the ontogeny of Ahr mRNA in mouse liver, and determine the epigenetic mechanisms regulating Ahr gene transcription during postnatal liver development. There was a 224% increase in hepatic Ahr mRNA from 2 days before birth to 45 days after birth. ChIP-on-chip analysis demonstrated that DNA methylation and histone H3K27 tri-methylation (H3K27Me3), two epigenetic marks for suppression of gene transcription, were consistently low around the Ahr gene locus. In contrast, enrichment of histone H3K4 di-methylation (H3K4Me2), a hallmark for gene activation, increased 182% from prenatal to young adult period around the Ahr gene locus. Regression analysis revealed a strong correlation between enrichment of H3K4Me2 and Ahr mRNA (r=0.91). In conclusion, postnatal H3K4Me2 enrichment positively associates with Ahr mRNA in developing mouse liver, providing a permissive chromatin state allowing Ahr gene transactivation in postnatal liver development.
Cui
Yue Julia
YJ
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Yeager
Ronnie L
RL
Zhong
Xiao-Bo
XB
Klaassen
Curtis D
CD
D000818:Animals; D015153:Blotting, Western; D021121:Branched DNA Signal Amplification Assay; D002843:Chromatin / Q000378:metabolism / Q000473:pathology; D003198:Computer Simulation; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D006657:Histones / Q000378:metabolism*; D008099:Liver / Q000254:growth & development* / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis* / Q000235:genetics; D012044:Regression Analysis
D002843:Chromatin; D006657:Histones; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon