Abstract
17β-estradiol (E2), the primary circulating estrogen hormone, mediates physiological and pathophysiological functions of breast tissue mainly through estrogen receptor α (ERα). Upon binding to E2, ERα modulates the expression of target genes involved in the regulation of cellular proliferation primarily through interactions with specific DNA sequences, estrogen response elements (EREs). Our previous microarray results suggested that E2-ERα modulates CXXC5 expression. Because of the presence of a zinc-finger CXXC domain (ZF-CXXC), CXXC5 is considered to be a member of the ZF-CXXC family, which binds to non-methylated CpG dinucleotides. Although studies are limited, CXXC5 appears to participate as a transcription factor, co-regulator and/or epigenetic factor in the regulation of cellular events induced by various signaling pathways. However, how signaling pathways mediate the expression of CXXC5 is yet unclear. Due to the importance of E2-ERα signaling in breast tissue, changes in the CXXC5 transcription/synthesis could participate in E2-mediated cellular events as well. To address these issues, we initially examined the mechanism whereby E2-ERα regulates CXXC5 expression. We show here that CXXC5 is an E2-ERα responsive gene regulated by the interaction of E2-ERα with an ERE present at a region upstream of the initial translation codon of the gene.
Highlights
After synthesis dimerizes and translocates predominantly to the nucleus independent of E23
We wanted to verify with RT-qPCR that the expression of CXXC5 is mediated by E2 signaling in cells synthesizing estrogen receptor α (ERα)
In assessing the mechanism by which E2-ERαmediates the CXXC5 gene expression in a cell model derived from breast adenocarcinoma, we show here that E2-ERαregulates the transcription of CXXC5 by a direct interaction with an estrogen response elements (EREs) sequence present at a region upstream of the initial translation codon of the CXXC5 locus
Summary
After synthesis dimerizes and translocates predominantly to the nucleus independent of E23. The transcriptional modulation of target genes through interaction of E2-ERαwith transcription factors bound to their cognate regulatory elements on DNA denotes the ERE-independent signaling pathway[2,8]. ZF-CXXC family proteins recognize and bind to non-methylated CpG containing DNA, concentrated in regions known as CpG islands[15] This binding is suggested to prevent DNA methylation leading to a state permissive to transcription[15]. Structural and functional studies on CXXC5 are limited It appears that CXXC5 expressed in different tissues at varying levels[12] is involved in the modulation of cellular proliferation, differentiation and death as a transcription factor, transcription co-regulator and/or chromatin modifier in response to retinoic acid, bone morphogenetic protein 4 (BMP4), Wnt signaling as well as to hypoxia[12,13,14,16,17]. Our results indicate that CXXC5 is a bona fide E2-ERαresponsive gene such that E2-ERαregulates the expression of CXXC5 through a direct interaction with an ERE sequence present at a region upstream of the initial translation codon of CXXC5
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
