Browsing by Subject "Promoter Regions, Genetic"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Evaluation of aldehyde dehydrogenase 1 promoter polymorphisms identified in human populations
    (Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2003-09) Spence, John P.; Liang, Tiebing; Eriksson, C. J. Peter; Taylor, Robert E.; Wall, Tamara L.; Ehlers, Cindy L.; Carr, Lucinda G.; Department of Medicine, IU School of Medicine
    BACKGROUND: Cytosolic aldehyde dehydrogenase, or ALDH1A1, functions in ethanol detoxification, metabolism of neurotransmitters, and synthesis of retinoic acid. Because the promoter region of a gene can influence gene expression, the ALDH1A1 promoter regions were studied to identify polymorphism, to assess their functional significance, and to determine whether they were associated with a risk for developing alcoholism. METHODS: Sequence analysis was performed in the promoter region by using Asian, Caucasian, and African American subjects. The resulting polymorphisms were assessed for frequency in Asian, Caucasian, Jewish, and African American populations and tested for associations with alcohol dependence in Asian and African American populations of alcoholics and controls. The functional significance of each polymorphism was determined through in vitro expression analysis by using HeLa and HepG2 cells. RESULTS: Two polymorphisms, a 17 base pair (bp) deletion (-416/-432) and a 3 bp insertion (-524), were discovered in the ALDH1A1 promoter region: ALDH1A1*2 and ALDH1A1*3, respectively. ALDH1A1*2 was observed at frequencies of 0.035, 0.023, 0.023, and 0.012 in the Asian, Caucasian, Jewish, and African American populations, respectively. ALDH1A1*3 was observed only in the African American population, at a frequency of 0.029. By using HeLa and HepG2 cells for in vitro expression, the activity of the luciferase reporter gene was significantly decreased after transient transfection of ALDH1A1*3-luciferase compared with the wild-type construct ALDH1A1*1-luciferase. In an African American population, a trend for higher frequencies of the ALDH1A1*2 and ALDH1A1*3 alleles was observed in a population of alcoholics (p = 0.03 and f = 0.12, respectively) compared with the control population. CONCLUSIONS: ALDH1A1*2 and ALDH1A1*3 may influence ALDH1A1 gene expression. Both ALDH1A1*2 and ALDH1A1*3 produce a trend in an African American population that may be indicative of an association with alcoholism; however, more samples are required to validate this observation. The underlying mechanisms contributing to these trends are still unknown.
  • Thumbnail Image
    Item
    HIF-transcribed p53 chaperones HIF-1α
    (Oxford University Press, 2019-11-04) Madan, Esha; Parker, Taylor M.; Pelham, Christopher J.; Palma, Antonio M.; Peixoto, Maria L.; Nagane, Masaki; Chandaria, Aliya; Tomás, Ana R.; Canas-Marques, Rita; Henriques, Vanessa; Galzerano, Antonio; Cabral-Teixeira, Joaquim; Selvendiran, Karuppaiyah; Kuppusamy, Periannan; Carvalho, Carlos; Beltran, Antonio; Moreno, Eduardo; Pati, Uttam K.; Gogna, Rajan; Surgery, School of Medicine
    Chronic hypoxia is associated with a variety of physiological conditions such as rheumatoid arthritis, ischemia/reperfusion injury, stroke, diabetic vasculopathy, epilepsy and cancer. At the molecular level, hypoxia manifests its effects via activation of HIF-dependent transcription. On the other hand, an important transcription factor p53, which controls a myriad of biological functions, is rendered transcriptionally inactive under hypoxic conditions. p53 and HIF-1α are known to share a mysterious relationship and play an ambiguous role in the regulation of hypoxia-induced cellular changes. Here we demonstrate a novel pathway where HIF-1α transcriptionally upregulates both WT and MT p53 by binding to five response elements in p53 promoter. In hypoxic cells, this HIF-1α-induced p53 is transcriptionally inefficient but is abundantly available for protein-protein interactions. Further, both WT and MT p53 proteins bind and chaperone HIF-1α to stabilize its binding at its downstream DNA response elements. This p53-induced chaperoning of HIF-1α increases synthesis of HIF-regulated genes and thus the efficiency of hypoxia-induced molecular changes. This basic biology finding has important implications not only in the design of anti-cancer strategies but also for other physiological conditions where hypoxia results in disease manifestation.
  • Thumbnail Image
    Item
    PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes
    (Oxford University Press, 2017-10-01) Singh, Deepak K.; Gholamalamdari, Omid; Jadaliha, Mahdieh; Li, Xiao Ling; Lin, Yo-Chuen; Zhang, Yang; Guang, Shuomeng; Hashemikhabir, Seyedsasan; Tiwari, Saumya; Zhu, Yuelin J.; Khan, Abid; Thomas, Anu; Chakraborty, Arindam; Macias, Virgilia; Balla, Andre K.; Bhargava, Rohit; Janga, Sarath Chandra; Ma, Jian; Prasanth, Supriya G.; Lal, Ashish; Prasanth, Kannanganattu V.; BioHealth Informatics, School of Informatics and Computing
    Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in BC initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in BC progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma. Survival data analyses revealed that the levels of PSIP1 showed a negative association with TNBC patient survival. Depletion of PSIP1/p75 significantly reduced the tumorigenicity and metastatic properties of TNBC cell lines while its over-expression promoted tumorigenicity. Further, gene expression studies revealed that PSIP1 regulates the expression of genes controlling cell-cycle progression, cell migration and invasion. Finally, by interacting with RNA polymerase II, PSIP1/p75 facilitates the association of RNA pol II to the promoter of cell cycle genes and thereby regulates their transcription. Our findings demonstrate an important role of PSIP1/p75 in TNBC tumorigenicity by promoting the expression of genes that control the cell cycle and tumor metastasis.
  • Thumbnail Image
    Item
    Regulation of the hepatitis B virus X gene promoters
    (1997) Khuntirat, Benjawan
  • Thumbnail Image
    Item