Disease relevance of Gene Expression Regulation

• The Ptch mutant mice provide the first mouse model, to our knowledge, of ultraviolet and ionizing radiation-induced basal cell carcinoma-like tumors, and also demonstrate that Ptch inactivation and hedgehog target gene activation are essential for basal cell carcinoma tumorigenesis [1].
• In vivo regulation of gene expression was demonstrated following co-injection of two separate recombinant adeno-associated virus vectors, one encoding an inducible murine erythropoietin transgene and the other a transcriptional activator, directly into the skeletal muscle of adult immunocompetent mice [2].
• Artificial regulation of gene expression in Escherichia coli by RNase P [3].
• Taken together, these results define a paradigm for estrogen action in breast cancer cells and suggest that regulation of gene expression by nuclear receptors can be compartmentalized into unique transcriptional domains by means of licensing of their activity to cofactors such as FOXA1 [4].
• They also raise the possibility of adverse side effects of GM-CSF therapy in patients whose malignant cells may be directly stimulated by this molecule and suggest a previously unanticipated role of GM-CSF gene activation in the evolution of solid tumors and in the pathogenesis of myelofibrosis [5].

Psychiatry related information on Gene Expression Regulation

• Myelin gene activation: a glucose sensitive critical period in development [6].
• Since a long-term administration of antidepressant drugs and mood stabilizers is required in the treatment of mood disorders, the regulation of gene expression by these drugs that is mediated by transcription factors, such as activator protein-1 (AP-1) complex, may play an important role in the therapeutic action [7].
• Regulation of gene expression by dopamine: implications in drug addiction [8].
• This review on the genes implicated in mental retardation, and its X-chromosome linked forms, we presented at the symposium 'The Regulation of Gene Expression in the Brain' (January 23-26, 2003, Heron Island Australia) [9].

High impact information on Gene Expression Regulation

• The study of RFX and CIITA has made major contributions to our comprehension of the molecular mechanisms controlling MHCII genes and has made this system into a textbook model for the regulation of gene expression [10].
• Over periods of minutes to hours, the amplitude, duration, and kinetic signature of Ca(2+) signals increase the efficiency and specificity of gene activation events [11].
• Recent data provide evidence that NF-kappa B is constitutively active in several cell types, potentially playing unexpected roles in regulation of gene expression [12].
• DNA methylation has a role in the regulation of gene expression during normal mammalian development but can also mediate epigenetic silencing of CpG island genes in cancer and other diseases [13].
• Furthermore, Htz1 promotes full gene activation but does not generally impact repression [14].

Chemical compound and disease context of Gene Expression Regulation

• To explain how induction of HO-1 results in protection against oxygen toxicity, hamster fibroblasts (HA-1) were stably transfected with a tetracycline response plasmid containing the full-length rat HO-1 cDNA construct to allow for regulation of gene expression by varying concentrations of doxycycline (Dox) [15].
• Fetal hemoglobin gene activation in a phase II study of 5,6-dihydro-5-azacytidine for bronchogenic carcinoma [16].
• The increased MNase sensitivity of the adult beta-globin gene region, normally preceded by the acquisition of 5' DNase I hypersensitivity, was blocked by the addition of imidazole prior to but not after globin gene activation [17].
• Nevertheless, for some genes a reduced response to hypoxia and desferrioxamine persisted in these mutant cells, clearly distinguishing ARNT/HIF-1beta-dependent and ARNT/HIF-1beta-independent mechanisms of gene activation by both these stimuli [18].
• Understanding androgen regulation of gene expression is critical for deciphering mechanisms responsible for the transition from androgen-responsive (AR) to androgen-independent (AI) prostate cancer (PCa) [19].

Biological context of Gene Expression Regulation

• Mechanistically, estrogen receptor induces changes in gene expression through direct gene activation and also through the biological functions of target loci [20].
• Cytosine methylation of mammalian DNA is essential for the proper epigenetic regulation of gene expression and maintenance of genomic integrity [21].
• Unexpectedly, the cbf1 null mutation concomitantly resulted in a methionine auxotrophic phenotype, which suggests that CBF1, like other HLH proteins in higher eukaryotic cells, participates in the regulation of gene expression [22].
• In transient transfection assays, RHA was found to cooperate with CBP in mediating target gene activation via the CAMP responsive factor CREB [23].
• The human proto-oncogene product, c-Jun, is a member of the AP-1 family of transcription factors, which mediate the regulation of gene expression in response to extracellular signaling [24].

Anatomical context of Gene Expression Regulation

• Mecp2 is expressed at high levels in the postnatal brain, indicating that methylation-dependent regulation of gene expression may have a crucial role in the mammalian central nervous system [25].
• A rat calcitonin-producing medullary thyroid carcinoma (MTC) line was used as a model for definition of certain aspects in regulation of gene expression [26].
• The rat prolactin and growth hormone genes are expressed selectively in distinct cell types (lactotrophs and somatotrophs, respectively) of the anterior pituitary gland, reflecting differential mechanisms of gene activation or restriction, as a result of the interactions of multiple factors binding to these genes [27].
• We found that subthreshold concentrations of interferon-gamma (IFN-gamma), which did not activate macrophages, increased their sensitivity to subsequent IFN-gamma stimulation; this resulted in increased signal transducer and activator of transcription 1 (STAT1) activation and increased IFN-gamma#150;dependent gene activation [28].
• The recent identification of the NFAT-interacting protein NIP45 as a methylated protein by marks a new role for protein arginine methylation in lymphocyte signaling and cytokine gene activation [29].

Associations of Gene Expression Regulation with chemical compounds

• The specificity of target gene activation by steroid receptors is encoded within a small, cysteine-rich domain that is believed to form two zinc-coordinated fingers [30].
• In animal cells, the v-erbA protein fails to respond to hormone and acts as a dominant negative allele, inhibiting gene activation normally conferred by the wild-type thyroid hormone receptor [31].
• All disease-associated alleles analysed had missense mutations and encoded proteins with an inactive tyrosine kinase, preventing downstream gene activation [32].
• Pretreatment with high concentrations of cycloheximide did not block calcitonin-induced PA-mRNA synthesis, indicating that PA gene activation was a primary transcriptional result of calcitonin stimulation and did not require new protein synthesis [33].
• 5-Azacytidine permits gene activation in a previously noninducible cell type [34].

Gene context of Gene Expression Regulation

• These studies thus define diverse cofactor functions, as well as underlying mechanisms involving distinct histone modifications, in p53-dependent gene activation [35].
• Very large portions of GAL4 are not required for gene activation [36].
• Our findings suggest that Gdf1 acts early in the pathway of gene activation that leads to the establishment of left-right asymmetry [37].
• Gene activation and DNA binding by Drosophila Ubx and abd-A proteins [38].
• From these observations and further analyses of GAL11, we propose that a single activator-holoenzyme contact can trigger gene activation simply by recruiting the latter to DNA [39].

Analytical, diagnostic and therapeutic context of Gene Expression Regulation

• Furthermore, in DNA microarray analysis, regulation of gene expression stimulated by prostaglandin E2 and UTP was not observed in cells lacking Gbeta-subunits [40].
• IFN-alpha-induced signaling and gene activation were inhibited by ligation of Fc receptors and Toll-like receptors 7 and 8 in a PKCbeta-dependent manner [41].
• Northern blot analysis showed that WAF1 gene activation by acidic conditions only occurred in A-172 cells [42].
• Culture of embryos with inhibitors of histone deacetylase trichostatin A and trapoxin results in an increase in the (1) amount of acetylated histone H4 detected by immunoblotting, (2) intensity and sharpness of the peripheral staining for H4.Ac5-12, and (3) relative rate of synthesis of proteins that are markers for zygotic gene activation [43].
• Experimental approaches designed to elucidate the molecular mechanisms of auxin action have focused on auxin perception, genetic dissection of the signaling apparatus and specific gene activation [44].

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4. From the Cover: Location analysis of estrogen receptor alpha target promoters reveals that FOXA1 defines a domain of the estrogen response. Laganière, J., Deblois, G., Lefebvre, C., Bataille, A.R., Robert, F., Giguère, V. Proc. Natl. Acad. Sci. U.S.A. (2005)
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14. Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss. Zhang, H., Roberts, D.N., Cairns, B.R. Cell (2005)
15. Reversal of HO-1 related cytoprotection with increased expression is due to reactive iron. Suttner, D.M., Dennery, P.A. FASEB J. (1999)
16. Fetal hemoglobin gene activation in a phase II study of 5,6-dihydro-5-azacytidine for bronchogenic carcinoma. Carr, B.I., Rahbar, S., Doroshow, J.H., Blayney, D., Goldberg, D., Leong, L., Asmeron, Y. Cancer Res. (1987)
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18. The role of the aryl hydrocarbon receptor nuclear translocator (ARNT) in hypoxic induction of gene expression. Studies in ARNT-deficient cells. Wood, S.M., Gleadle, J.M., Pugh, C.W., Hankinson, O., Ratcliffe, P.J. J. Biol. Chem. (1996)
19. Gene expression profiling identifies a unique androgen-mediated inflammatory/immune signature and a PTEN (phosphatase and tensin homolog deleted on chromosome 10)-mediated apoptotic response specific to the rat ventral prostate. Desai, K.V., Michalowska, A.M., Kondaiah, P., Ward, J.M., Shih, J.H., Green, J.E. Mol. Endocrinol. (2004)
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22. Yeast centromere binding protein CBF1, of the helix-loop-helix protein family, is required for chromosome stability and methionine prototrophy. Cai, M., Davis, R.W. Cell (1990)
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24. Biochemical analysis of transcriptional activation by Jun: differential activity of c- and v-Jun. Bohmann, D., Tjian, R. Cell (1989)
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30. Two amino acids within the knuckle of the first zinc finger specify DNA response element activation by the glucocorticoid receptor. Danielsen, M., Hinck, L., Ringold, G.M. Cell (1989)
31. The viral erbA oncogene protein, a constitutive repressor in animal cells, is a hormone-regulated activator in yeast. Privalsky, M.L., Sharif, M., Yamamoto, K.R. Cell (1990)
32. Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema. Karkkainen, M.J., Ferrell, R.E., Lawrence, E.C., Kimak, M.A., Levinson, K.L., McTigue, M.A., Alitalo, K., Finegold, D.N. Nat. Genet. (2000)
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34. 5-Azacytidine permits gene activation in a previously noninducible cell type. Chiu, C.P., Blau, H.M. Cell (1985)
35. Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53. An, W., Kim, J., Roeder, R.G. Cell (2004)
36. Deletion analysis of GAL4 defines two transcriptional activating segments. Ma, J., Ptashne, M. Cell (1987)
37. Regulation of left-right patterning in mice by growth/differentiation factor-1. Rankin, C.T., Bunton, T., Lawler, A.M., Lee, S.J. Nat. Genet. (2000)
38. Gene activation and DNA binding by Drosophila Ubx and abd-A proteins. Samson, M.L., Jackson-Grusby, L., Brent, R. Cell (1989)
39. Contact with a component of the polymerase II holoenzyme suffices for gene activation. Barberis, A., Pearlberg, J., Simkovich, N., Farrell, S., Reinagel, P., Bamdad, C., Sigal, G., Ptashne, M. Cell (1995)
40. Silencing the expression of multiple Gbeta-subunits eliminates signaling mediated by all four families of G proteins. Hwang, J.I., Choi, S., Fraser, I.D., Chang, M.S., Simon, M.I. Proc. Natl. Acad. Sci. U.S.A. (2005)
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42. p53-dependent induction of WAF1 by a low-pH culture condition in human glioblastoma cells. Ohtsubo, T., Wang, X., Takahashi, A., Ohnishi, K., Saito, H., Song, C.W., Ohnishi, T. Cancer Res. (1997)
43. Temporally restricted spatial localization of acetylated isoforms of histone H4 and RNA polymerase II in the 2-cell mouse embryo. Worrad, D.M., Turner, B.M., Schultz, R.M. Development (1995)
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