VTechWorks staff will be away for the Independence Day holiday from July 4-7. We will respond to email inquiries on Monday, July 8. Thank you for your patience.
 

The mechanism of transactivation regulation due to polymorphic short tandem repeats (STRs) using IGF1 promoter as a model

Simple item page
dc.contributor.authorChen, Holly Y.en
dc.contributor.authorMa, Suk Lingen
dc.contributor.authorHuang, Weien
dc.contributor.authorJi, Lindanen
dc.contributor.authorLeung, Vincent H. K.en
dc.contributor.authorJiang, Honglinen
dc.contributor.authorYao, Xiaoqiangen
dc.contributor.authorTang, Nelson L. S.en
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.date.accessioned2019-01-18T15:45:12Zen
dc.date.available2019-01-18T15:45:12Zen
dc.date.issued2016-12-02en
dc.description.abstractFunctional short tandem repeats (STR) are polymorphic in the population, and the number of repeats regulates the expression of nearby genes (known as expression STR, eSTR). STR in IGF1 promoter has been extensively studied for its association with IGF1 concentration in blood and various clinical traits and represents an important eSTR. We previously used an in-vitro luciferase reporter model to examine the interaction between STRs and SNPs in IGF1 promoter. Here, we further explored the mechanism how the number of repeats of the STR regulates gene transcription. An inverse correlation between the number of repeats and the extent of transactivation was found in a haplotype consisting of three promoter SNPs (C-STR-T-T). We showed that these adjacent SNPs located outside the STR were required for the STR to function as eSTR. The C allele of rs35767 provides a binding site for CCAAT/enhancer-binding-protein delta (C/EBPD), which is essential for the gradational transactivation property of eSTR and FOXA3 may also be involved. Therefore, we propose a mechanism in which the gradational transactivation by the eSTR is caused by the interaction of one or more transcriptional complexes located outside the STR, rather than by direct binding to a repeat motif of the STR.en
dc.description.notesWe hereby thank all the members in our lab for their discussions on this project and Miss LO Pui Shan for preparing the typeset of the manuscript. The work was supported by NSFC (31171213 & 81402747), Shenzhen Science and Technology Innovation Committee (GJHS20120702105523299) and grant from CUHK's Shenzhen Development Office.en
dc.description.sponsorshipNSFC [31171213, 81402747]; Shenzhen Science and Technology Innovation Committee [GJHS20120702105523299]; CUHK's Shenzhen Development Officeen
dc.format.extent10en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/srep38225en
dc.identifier.issn2045-2322en
dc.identifier.other38225en
dc.identifier.pmid27910883en
dc.identifier.urihttp://hdl.handle.net/10919/86755en
dc.identifier.volume6en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectbreast-cancer risken
dc.subjectgrowth-factor 1en
dc.subjectgene-expressionen
dc.subjecthuman genomeen
dc.subjecttranscriptional regulationen
dc.subjectmammographic densityen
dc.subjectmultiethnic cohorten
dc.subjectprostate-canceren
dc.subjectcore promoteren
dc.subjectmicrosatellitesen
dc.titleThe mechanism of transactivation regulation due to polymorphic short tandem repeats (STRs) using IGF1 promoter as a modelen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
srep38225.pdf
Size:
810.09 KB
Format:
Adobe Portable Document Format
Description:
Download

Collections

Scholarly Works, School of Animal Sciences