Counter regulation of ECRG4 gene expression by hypermethylation-dependent inhibition and the Sp1 transcription factor-dependent stimulation of the c2orf40 promoter.

Counter regulation of ECRG4 gene expression by hypermethylation-dependent inhibition and the Sp1 transcription factor-dependent stimulation of the c2orf40 promoter. Gene. 2017 Sep 01;: Authors: Dang X, Zeng X, Coimbra R, Eliceiri BP, Baird A Abstract The human cytokine precursor ECRG4 has been associated with multiple physiological, developmental and pathophysiological processes involving cell proliferation, cell migration, innate immunity, inflammation, cancer progression and metastases. Although down-regulation of ECRG4 gene expression has been largely attributed to hypermethylation of CpG islands in the 5'untranslated region of the ECRG4 promoter, the mechanisms that underlie the dynamics of its regulation have never been systematically described. Here we show that the ECRG4 gene is widely expressed in human tissues and report that its core promoter lies between the -780 to +420 base pairs relative to the ATG start codon of the ECRG4 open reading frame. This sequence, which contains several CpG islands, also includes multiple overlapping Sp1 consensus binding sequences and a putative binding site for NF-kB activation. 5'RACE of mRNA derived from human leukocytes shows that ECRG4 transcription initiates from the guanidine at -11 from the initiation ATG of the ECRG4 open reading frame. While there is no canonical TATA- or CAAT-boxes proximal to this translational initiation site, there is a distal TATA-sequence in the 5'UTR. This re...
Source: Gene - Category: Genetics & Stem Cells Authors: Tags: Gene Source Type: research