The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR

Sugatani, Junko

doi:10.1053/jhep.2001.24172

Cited by 335 publications

(251 citation statements)

References 22 publications

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“…UGT1A gene products are generated by a strategy of exon sharing, resulting in divergent isoforms with a unique N-terminal domain and commonly shared C-terminal 245 amino acids. As UGT proteins are detoxifying enzymes, it is natural that this gene expression is regulated by xenobiotic receptor including pregnenolone X receptor and constitutive androstane receptor (Sugatani et al, 2001;Xie et al, 2003). Reduction of UGT1A expression is involved in the early phase of neoplastic transformation, such as in liver and biliary cancer, bladder cancer and colon cancer (Strassburg et al, 1997;Giuliani et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis

et al. 2007

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The androgen receptor (AR) plays a key role as a transcriptional factor in prostate development and carcinogenesis. Identification of androgen-regulated genes is essential to elucidate the AR pathophysiology in prostate cancer. Here, we identified androgen target genes that are directly regulated by AR in LNCaP cells, by combining chromatin immunoprecipitation (ChIP) with tiling microarrays (ChIP-chip). ChIP-enriched or control DNAs from the cells treated with R1881 were hybridized with the ENCODE array, in which a set of regions representing approximately 1% of the whole genome. We chose 10 bona fide AR-binding sites (ARBSs) (Po1e-5) and validated their significant AR recruitment ligand dependently. Eight upregulated genes by R1881 were identified in the vicinity of the ARBSs. Among the upregulated genes, we focused on UGT1A and CDH2 as AR target genes, because the ARBSs close to these genes (in UGT1A distal promoter and CDH2 intron 1) were most significantly associated with acetylated histone H3/H4, RNA polymerase II and p160 family co-activators. Luciferase reporter constructs including those two ARBSs exhibited ligand-dependent transcriptional regulator/enhancer activities. The present study would be powerful to extend our knowledge of the diversity of androgen genetic network and steroid action in prostate cancer cells.

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Section: Discussionmentioning

confidence: 99%

Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis

et al. 2007

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“…In fact, Crigler-Najjar syndromes I and II habe been distinguished on the basis of phenobarbital induction of UGT1A1 [45]. CAR/RXR-binding domains were first identified in studies of UGT1A1 regulation [46,47], the only UGT responsible for bilirubin clearance in humans. Interestingly, the CAR-binding domain resides in a 290 base pair cluster, termed gtPBREM (glucuronosyltransferase PhenobarbitalResponsive Enhancer Module), discussed in section 4.2.…”

Section: Car and Pxrmentioning

confidence: 99%

“…It is tempting to speculate that evolution of the gtPBREM cluster of binding sites for a number of LATFs in the promoter of UGT1A1 [46,47] may be related to the need for perinatal UGT1A1 induction in primates. This cluster contains binding sites for CAR and PXR [47], AhR [33], Nrf2 [76], PPARα [51] and for the glucocorticoid receptor [47].…”

Section: Page 9 Of 31mentioning

confidence: 99%

From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans

Bock¹

2011

Biochemical Pharmacology

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. From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans. Biochemical Pharmacology, Elsevier, 2011, 82 (1) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64

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“…Of note, segment I extends upstream to include the phenobarbital response enhancer module 5 0 of UGT1A1. 35 The region labeled 3 0 represents the sum of four segments in the 3 0 end portion of the gene cluster, which contains the shared exons coding for the enzyme C-terminus. The segments coincide with conserved non-coding sequence 5 0 to the exons, exons 2-4, exon 5, and a region of 3 0 conserved non-coding sequence.…”

Section: Multispecies Comparative Genomics Of Ugt1amentioning

confidence: 99%

Comparative genomics analysis of human sequence variation in the UGT1A gene cluster

et al. 2005

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Common polymorphisms within the human UGT1A gene locus are associated with irinotecan and tranilast toxicity. To uncover additional functional variation across this gene cluster, cross-species sequence comparisons were performed. Evolutionarily conserved segments (a total of 47.1 kb) were re-sequenced in 24 African-American, 24 European-American, and 24 Asian individuals, and 381 segregating sites (including 123 singletons) were identified. Highly conserved coding sites were less likely to be polymorphic than diverged sites (Po0.0001) but this pattern was not observed at noncoding sites (P ¼ 0.1025). Among coding variants, the distribution of those computationally predicted to affect function was skewed toward low frequencies. Some alleles occurred at similar frequencies in each population; others had wide disparities. Although strong linkage disequilibrium was detected among the hepatically expressed genes, the degree of linkage disequilibrium varied among populations. These results suggest that rare functional gene variants and inter-population variability must be considered in the interpretation of association studies between UGT1A and drug metabolism/toxicity phenotypes.

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The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR

Cited by 335 publications

References 22 publications

Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis

Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis

From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans

Comparative genomics analysis of human sequence variation in the UGT1A gene cluster

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