Disease relevance of GC Rich Sequence

• OBJECTIVE: To identify one nuclear autoantigenic protein within a complex of DNA binding proteins that bind to GC-rich sequences in Epstein-Barr virus and cellular DNA, and to describe the clinical characteristics of patients whose sera contained autoantibodies to this novel autoantigen [1].
• Previous studies have shown that the adenovirus 12S E1A oncoprotein represses the TGF-beta 1 promoter by targeting an adjacent (-90 to -81) but different GC-rich sequence (TGGGTGGGG) [2].
• Vent exo- resolves highly GC-rich sequence substantially better than Thermus aquaticus DNA polymerase (Taq) and with a similar efficiency as Pfu exo-. The DNA/DNA polymerase activity ratio is significantly higher for Vent exo- than for Pfu exo-, which is reflected by the sensibility of Vent exo- in efficiently amplifying genomic DNA [3].

High impact information on GC Rich Sequence

• We have cloned a human cDNA that encodes a factor that binds to the GC-rich sequences present in the epidermal growth factor receptor (EGFR), beta-actin, and calcium-dependent protease (CANP) promoters [4].
• Functional analysis of the 2.2 kb TF 5' promoter indicated that a GC-rich region containing three copies each of the EGR-1 and Sp1 sites was required for induction [5].
• Three cis-acting elements in the KAR2 promoter control expression of KAR2: (i) a GC-rich region that contributes to the high level of constitutive expression, (ii) a functional heat shock element (HSE) and (iii) an element (UPR) that is involved in the induction of BiP mRNA by unfolded proteins [6].
• However, in the most homologous region, a GC-rich sequence is inserted in the A. nidulans intron, flanked by two direct repeats of 5 bp [7].
• Other GC-rich sequences coding for some polyalanine domains were found to be polymorphic in human [8].

Biological context of GC Rich Sequence

• Methylation studies indicated that the tal-15' GC-rich region behaves like a CpG island, hypomethylated in normal cells, and methylated de novo on transcriptionally inactive alleles in established cell lines [9].
• We also found that LY294002 increases ATF3 promoter activity and the transactivation is partly mediated by a GC-rich sequence located in the promoter [10].
• Transfection experiments in HepG2 cells allowed to identify a silencer-like element containing putative HNF1 and HNF3 sites and activator elements containing stretches of GC-rich sequences [11].
• A typical "CCAAT" box sequence is not present in the adjacent 5'-flanking region; however, there is a GC-rich sequence (at nucleotide -215) similar to the binding site for the nuclear transcription factor Sp1 [12].
• Because the removal of the 8-bp consensus TATATATA at -399 to -406 and CCAAT at -410 to -414 did not significantly affect the transcription efficiency of the promoter, GC-rich sequences between this TATA box and the translation start site may be very important for the promoter activity of the C1qBP gene [13].

Anatomical context of GC Rich Sequence

• The minimal region of the p21 promoter required for its induction in keratinocyte differentiation consists of a contiguous stretch of 78 base pairs, which contains a GC-rich region as well as the TATA box [14].
• Additional sites of protein binding included a region in the GC-rich sequences downstream of the 75-bp repeats (only in fibroblasts), a hypersensitive guanine on the minus strand in the LVc site (only in T-lymphoid cells), and a region upstream of the 75-bp repeats [15].
• Although the H1t/TE element that contains the GC-rich region binds nuclear proteins, it does not appear to bind Sp1 obtained from cell populations enriched in primary spermatocytes as determined by electrophoretic mobility supershift assays using polyclonal anti-Sp1 antibodies [16].
• Two regulatory regions, a consensus binding site for PU.1 and a GC-rich region, are required for basal IL-18 promoter activity in human myeloid cells [17].
• Thus, cAMP-induced transcription from the KL gene promoter in primary mouse Sertoli cells is mediated by a complex interaction among a Sp1-binding region, factors recognizing the canonical TATA box sequence, and a not yet identified cAMP-induced factor binding a GC-rich sequence just downstream from it [18].

Associations of GC Rich Sequence with chemical compounds

• Termination of transcription occurs at 5 consecutive thymine residues that are preceded by a GC-rich region [19].
• Here, we show that ETF recognizes various GC-rich sequences including stretches of deoxycytidine or deoxyguanosine residues and GC boxes with similar affinities [20].
• Analysis of the base pair sequences of pausing sites shows that pausing may result from the presence of dyad symmetry, GC-rich sequences, or (for inosine-substituted transcripts) C-rich sequences in the RNA-DNA hybrid region [21].
• The hyperoxia response was localized to a 7-base pair region between -62 and -55, which contained a GC-rich region consistent with a consensus sequence for the SP1 family, that was sufficient for up-regulation by hyperoxia [22].
• Transcription of the gene encoding this RNA species terminates within a stretch of 6 deoxythymidylic acid residues which are located 38 nucleotides beyond the predicted termination site for VA RNAI and which are preceded by a GC-rich sequence of nucleotides [23].

Gene context of GC Rich Sequence

• Lying between these two elements is a GC-rich region that is similar in sequence to the consensus element for binding of the mammalian transcription factor Sp1 and that is involved in the basal expression of the KAR2 gene [24].
• Three types of sites function independently of the nitrogen source: two clusters of Abflp- and Rap1p-binding sites, and a GC-rich sequence [25].
• Several lines of evidence show that CUGBP1 induces the translation of p21 via binding to a GC-rich sequence located within the 5' region of p21 mRNA [26].
• The results from transcription assays demonstrated that Vpr augments promoter activity of p21 through the GC-rich region located between nucleotides -84 and -74 with respect to the +1 transcription start site [27].
• Moreover, direct DNA binding of BMP-responsive Smads and common-partner Smad4 to the GC-rich sequence of PBE was observed [28].

Analytical, diagnostic and therapeutic context of GC Rich Sequence

• Using dimethyl sulfate in vivo footprinting via ligation-mediated PCR, we identified potentially important regions for HSD11B2 regulation in human cell lines: two GC-rich regions in the first exon (I and II) and two upstream elements (III and IV) [29].
• In addition, by electrophoretic mobility shift assays, supershift assays, and DNase I footprinting studies, we have detected the binding of the transcription factor Sp1 at the two GC-rich sequences located within the -340 to -249 region of promoter II [30].
• DNA footprinting of the TxRE with 1, 10-phenanthroline-copper complex demonstrates that Tax contacts DNA and extends the footprint of CREB to GC-rich sequences flanking the core CRE-like element [31].
• Interactions of nuclear proteins from ZR-75 cells with the proximal GC-rich region of the VEGF gene promoter were investigated by electrophoretic mobility shift and chromatin immunoprecipitation assays [32].
• Selectivity for GC-rich sequences was also indicated by CD titration studies [33].

References