PT  - JOURNAL ARTICLE
AU  - Ya-Li Nie
AU  - Xiang-Guang Meng
AU  - Jing-Yang Liu
AU  - Liang Yan
AU  - Pei Wang
AU  - Hong-Zheng Bi
AU  - Quan-Cheng Kan
AU  - Li-Rong Zhang
TI  - Histone Modifications Regulate the Developmental Expression of Human Hepatic UDP-Glucuronosyltransferase 1A1
AID  - 10.1124/dmd.117.076109
DP  - 2017 Dec 01
TA  - Drug Metabolism and Disposition
PG  - 1372--1378
VI  - 45
IP  - 12
4099  - http://dmd.aspetjournals.org/content/45/12/1372.short
4100  - http://dmd.aspetjournals.org/content/45/12/1372.full
SO  - Drug Metab Dispos2017 Dec 01; 45
AB  - Human UDP-glucuronosyltransferase 1A1 (UGT1A1) is a unique enzyme involved in bilirubin conjugation. We previously characterized the hepatic expression of transcription factors affecting UGT1A1 expression during development. Accordingly, in this study, we characterized the ontogenetic expression of hepatic UGT1A1 from the perspective of epigenetic regulation. We observed significant histone-3-lysine-4 dimethylation (H3K4me2) enrichment in the adult liver and histone-3-lysine-27 trimethylation (H3K27me3) enrichment in the fetal liver, indicating that dynamic alterations of histone methylation were associated with ontogenetic UGT1A1 expression. We further showed that the transcription factor hepatocyte nuclear factor 1α (HNF1A) affects histone modifications around the UGT1A1 locus. In particular, we demonstrated that by recruiting HNF1A the cofactors mixed-lineage leukemia 1, the transcriptional coactivator p300, and nuclear receptor coactivator 6 aggregate at the UGT1A1 promoter, thereby regulating histone modifications and subsequent UGT1A1 expression. In this study, we proposed new ideas for the developmental regulation of metabolic enzymes via histone modifications, and our findings will potentially contribute to the development of age-specific therapies.