Effect of metallothionein core promoter region polymorphism on Cu, Zn, Cr, Ni, Cd, Pb and as levels in autopsy lung tissues from a Turkish population

Activators of protein kinase C, such as 12-O-tetradecanoylphorbol 13-acetate (TPA), are known to regulate the expression of many genes, including the tumor necrosis factor alpha (TNF) gene, by affecting the level or activity of upstream transcription factors. To investigate the mechanism whereby TPA activates the TNF promoter, a series of 5'-deletion mutants of the human TNF promoter linked to chloramphenicol acetyltransferase was transfected into U937 human promonocytic cells. TPA produced a 7- to 11-fold activation of all TNF promoters tested, even those promoters truncated to contain only the core promoter with no upstream enhancer elements. The proximal TNF promoter containing only 28 nucleotides upstream and 10 nucleotides downstream of the RNA start site confers TPA activation to a variety of unrelated upstream enhancer elements and transcription factors, including Sp1, CTF/NF1, cyclic AMP-response element, GAL-E1a, and GAL-VP16. The level of activation by TPA depends on the TATA box structure, since the TPA response is greater in promoters containing the sequence TATAAA than in those containing TATTAA or TATTTA. These findings suggest that the core promoter region is a target for gene regulation by second-messenger pathways.

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The decapentaplegic core promoter region plays an integral role in the spatial control of transcription.

Molecular and Cellular Biology ◽

10.1128/mcb.15.7.3960 ◽

1995 ◽

Vol 15 (7) ◽

pp. 3960-3968 ◽

Cited By ~ 21

Author(s):

D H Schwyter ◽

J D Huang ◽

T Dubnicoff ◽

A J Courey

Keyword(s):

Expression Pattern ◽

Phase Ii ◽

Promoter Region ◽

Core Promoter ◽

Critical Role ◽

Regulatory Elements ◽

Drosophila Embryo ◽

Phase Iii ◽

Core Promoter Region ◽

Flanking Region

The Drosophila melanogaster decapentaplegic (dpp) gene encodes a transforming growth factor beta-related cell signaling molecule that plays a critical role in dorsal/ventral pattern formation. The dpp expression pattern in the Drosophila embryo is dynamic, consisting of three phases. Phase I, in which dpp is expressed in a broad dorsal domain, depends on elements in the dpp second intron that interact with the Dorsal transcription factor to repress transcription ventrally. In contrast, phases II and III, in which dpp is expressed first in broad longitudinal stripes (phase II) and subsequently in narrow longitudinal stripes (phase III), depend on multiple independent elements in the dpp 5'-flanking region. Several aspects of the normal dpp expression pattern appear to depend on the unique properties of the dpp core promoter. For example, this core promoter (extending from -22 to +6) is able to direct a phase II expression pattern in the absence of additional upstream or downstream regulatory elements. In addition, a ventral-specific enhancer in the dpp 5'-flanking region that binds the Dorsal factor activates the heterologous hsp70 core promoter but not the dpp core promoter. Thus, the dpp core promoter region may contribute to spatially regulated transcription both by interacting directly with spatially restricted activators and by modifying the activity of proteins bound to enhancer elements.

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High Frequency of Either Altered Pre-Core Start Codon or Weakened Kozak Sequence in the Core Promoter Region in Hepatitis B Virus A1 Strains from Rwanda

Genes ◽

10.3390/genes10030182 ◽

2019 ◽

Vol 10 (3) ◽

pp. 182 ◽

Cited By ~ 1

Author(s):

Heléne Norder ◽

Theogene Twagirumugabe ◽

Joanna Said ◽

Yarong Tian ◽

Ka-Wei Tang ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Promoter Region ◽

Core Promoter ◽

Etiologic Agent ◽

Start Codon ◽

Core Promoter Region ◽

Kozak Sequence ◽

The Core ◽

B Virus

Hepatitis B virus (HBV) is endemic in Rwanda and is a major etiologic agent for chronic liver disease in the country. In a previous analysis of HBV strains from Rwanda, the S genes of most strains segregated into one single clade of subgenotype, A1. More than half (55%) of the anti-HBe positive individuals were viremic. In this study, 23 complete HBV genomes and the core promoter region (CP) from 18 additional strains were sequenced. Phylogenetic analysis of complete genomes confirmed that most Rwandan strain formed a single unique clade, within subgenotype A1. Strains from 17 of 22 (77%) anti-HBe positive HBV carriers had either mutated the precore start codon (9 strains with either CUG, ACG, UUG, or AAG) or mutations in the Kozak sequence preceding the pre-core start codon (8 strains). These mutually exclusive mutations were also identified in subgenotypes A1 (70/266; 26%), A2 (12/255; 5%), and A3 (26/49; 53%) sequences from the GenBank. The results showed that previous, rarely described HBV variants, expressing little or no HBeAg, are selected in anti-HBe positive subgenotype Al carriers from Rwanda and that mutations reducing HBeAg synthesis might be unique for a particular HBV clade, not just for a specific genotype or subgenotype.

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