A novel transcriptional element which regulates expression of the CYP2D4 gene by Oct-1 and YY-1 binding

Mizuno, Dai; Takahashi, Yoshiki; Hiroi, Toyoko; Imaoka, Shingi; Kamataki, Tetsuya; Funae, Yoshihiko

doi:10.1016/s0167-4781(03)00085-x

Cited by 9 publications

(6 citation statements)

References 33 publications

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“…gambiae CYP6Zs (Nikou et al, 2003) and Musca domestica CYP6Ds (Kasai and Scott, 2000) may also suggest a possible role in the detoxification of xenobiotics. Finally, the identification of a short nucleotide sequence highly similar to the transcription regulatory element Oct, previously found to be associated with other herbivorous insect CYP6Bs (McDonnell et al, 2004) and mammalian CYP2Ds (Mizuno et al, 2003) may support the differential expression of CYP6AL1 gene in response to xenobiotic exposure. However, the full demonstration of the involvement of this gene in the adaptation to plant toxins found in decaying leaf litters will need the completion of the purification of those plant toxins and the evidence of their metabolisation in vitro by CYP6AL1 recombinant protein.…”

Section: Discussionmentioning

confidence: 76%

Involvement of cytochrome P450 monooxygenases in the response of mosquito larvae to dietary plant xenobiotics

David

Boyer

Mesneau

et al. 2006

Insect Biochemistry and Molecular Biology

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Section: Discussionmentioning

confidence: 76%

Involvement of cytochrome P450 monooxygenases in the response of mosquito larvae to dietary plant xenobiotics

David

Boyer

Mesneau

et al. 2006

Insect Biochemistry and Molecular Biology

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“…Inhibition of transcription by YY1 relates to its ability to form trans-repressing complexes with histone-modifying enzymes, in particular, HDAC1 (15,64). The repressor role of YY1 on key regulatory elements is often linked to competition for binding of positive acting factors to the same DNA, including among others the AP-1 complex (65) and Oct-1 (35). Interestingly, trans-repression by YY1 can be prevented by its interaction with nucleophosmin/B23, which is much more abundant in tumor or proliferating cells (11,23) and is activated by estrogens in MCF-7 and ZR-75.1 cells (13,54).…”

Section: Discussionmentioning

confidence: 99%

Estrogens and Progesterone Promote Persistent CCND1 Gene Activation during G₁ by Inducing Transcriptional Derepression via c-Jun/c-Fos/Estrogen Receptor (Progesterone Receptor) Complex Assembly to a Distal Regulatory Element and Recruitment of Cyclin D1 to Its Own Gene Promoter

Cicatiello

Addeo

Sasso

et al. 2004

Molecular and Cellular Biology

159

125

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Transcriptional activation of the cyclin D1 gene (CCND1) plays a pivotal role in G 1 -phase progression, which is thereby controlled by multiple regulatory factors, including nuclear receptors (NRs). Appropriate CCND1 gene activity is essential for normal development and physiology of the mammary gland, where it is regulated by ovarian steroids through a mechanism(s) that is not fully elucidated. We report here that CCND1 promoter activation by estrogens in human breast cancer cells is mediated by recruitment of a c-Jun/c-Fos/estrogen receptor ␣ complex to the tetradecanoyl phorbol acetate-responsive element of the gene, together with Oct-1 to a site immediately adjacent. This process coincides with the release from the same DNA region of a transcriptional repressor complex including Yin-Yang 1 (YY1) and histone deacetylase 1 and is sufficient to induce the assembly of the basal transcription machinery on the promoter and to lead to initial cyclin D1 accumulation in the cell. Later on in estrogen stimulation, the cyclin D1/Cdk4 holoenzyme associates with the CCND1 promoter, where E2F and pRb can also be found, contributing to the long-lasting gene enhancement required to drive G 1 -phase completion. Interestingly, progesterone triggers similar regulatory events through its own NRs, suggesting that the gene regulation cascade described here represents a crossroad for the transcriptional control of G 1 -phase progression by different classes of NRs.Mammary gland morphogenesis and development result from the interplay of genetic and epigenetic pathways, controlled by hormones, growth factors, and other signaling molecules. Derangement of one or more of these regulatory pathways results in the abnormal growth and differentiation of mammary epithelial cells, leading to breast carcinogenesis. The ovarian hormones estrogen and progesterone promote mammary gland differentiation toward the female phenotype at the onset of puberty and control breast tropism and function throughout the reproductive life by affecting epithelial cell proliferation. Mammary gland cells are endowed with highaffinity receptors for these steroids (estrogen receptor ␣ [ER␣] and ER␤ and progesterone receptor A [PR-A] and PR-B, respectively), which belong to the nuclear receptor (NR) family of transcription factors (31

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“…64 transcription regulators overlapped between the two platforms (Gene List 1). Among the 64 transcription factors predicted mediateding genetic regulation of CYP2D6 activity, YY1 is reported putatively binding to gene CYP2D6 promoter region and regulating the expression of CYP2D6 and CYP2D4 [28, 29]. …”

Section: Resultsmentioning

confidence: 99%

New aQTL SNPs for the CYP2D6 Identified by a Novel Mediation Analysis of Genome-Wide SNP Arrays, Gene Expression Arrays, and CYP2D6 Activity

Jiang

Chakraborty

Wang

et al. 2013

BioMed Research International

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Background. The genome-wide association studies (GWAS) have been successful during the last few years. A key challenge is that the interpretation of the results is not straightforward, especially for transacting SNPs. Integration of transcriptome data into GWAS may provide clues elucidating the mechanisms by which a genetic variant leads to a disease. Methods. Here, we developed a novel mediation analysis approach to identify new expression quantitative trait loci (eQTL) driving CYP2D6 activity by combining genotype, gene expression, and enzyme activity data. Results. 389,573 and 1,214,416 SNP-transcript-CYP2D6 activity trios are found strongly associated (P < 10−5, FDR = 16.6% and 11.7%) for two different genotype platforms, namely, Affymetrix and Illumina, respectively. The majority of eQTLs are trans-SNPs. A single polymorphism leads to widespread downstream changes in the expression of distant genes by affecting major regulators or transcription factors (TFs), which would be visible as an eQTL hotspot and can lead to large and consistent biological effects. Overlapped eQTL hotspots with the mediators lead to the discovery of 64 TFs. Conclusions. Our mediation analysis is a powerful approach in identifying the trans-QTL-phenotype associations. It improves our understanding of the functional genetic variations for the liver metabolism mechanisms.

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A novel transcriptional element which regulates expression of the CYP2D4 gene by Oct-1 and YY-1 binding

Cited by 9 publications

References 33 publications

Involvement of cytochrome P450 monooxygenases in the response of mosquito larvae to dietary plant xenobiotics

Involvement of cytochrome P450 monooxygenases in the response of mosquito larvae to dietary plant xenobiotics

Estrogens and Progesterone Promote Persistent CCND1 Gene Activation during G₁ by Inducing Transcriptional Derepression via c-Jun/c-Fos/Estrogen Receptor (Progesterone Receptor) Complex Assembly to a Distal Regulatory Element and Recruitment of Cyclin D1 to Its Own Gene Promoter

New aQTL SNPs for the CYP2D6 Identified by a Novel Mediation Analysis of Genome-Wide SNP Arrays, Gene Expression Arrays, and CYP2D6 Activity

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A novel transcriptional element which regulates expression of the CYP2D4 gene by Oct-1 and YY-1 binding

Cited by 9 publications

References 33 publications

Involvement of cytochrome P450 monooxygenases in the response of mosquito larvae to dietary plant xenobiotics

Involvement of cytochrome P450 monooxygenases in the response of mosquito larvae to dietary plant xenobiotics

Estrogens and Progesterone Promote Persistent CCND1 Gene Activation during G1 by Inducing Transcriptional Derepression via c-Jun/c-Fos/Estrogen Receptor (Progesterone Receptor) Complex Assembly to a Distal Regulatory Element and Recruitment of Cyclin D1 to Its Own Gene Promoter

New aQTL SNPs for the CYP2D6 Identified by a Novel Mediation Analysis of Genome-Wide SNP Arrays, Gene Expression Arrays, and CYP2D6 Activity

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Estrogens and Progesterone Promote Persistent CCND1 Gene Activation during G₁ by Inducing Transcriptional Derepression via c-Jun/c-Fos/Estrogen Receptor (Progesterone Receptor) Complex Assembly to a Distal Regulatory Element and Recruitment of Cyclin D1 to Its Own Gene Promoter