PP137. HUMAN SOX3 GENE: MAPPING OF THE ELEMENTS INVOLVED IN RETINOIC ACID INDUCED TRANSCRIPTIONAL ACTIVATION
G. NIKČEVIĆ; M. Mojsin; N. Kovačević Grujičić; A. Krstić; T. Savić, M. Stevanović Institute of Molecular Genetics and Genetic Engineering, Belgrade, Serbia e-mail: gordnik@eunet.yu
*Corresponding Author:
page: 109

Abstract

Sox3/SOX3 gene is implicated in the control of nervous system development and is considered to be one of the earliest neural markers. Previously, we have reported that human SOX3 gene is transcriptionally up-regulated during retinoic acid (RA)-induced differentiation of NT2/D1 embryonal carcinoma cell line. Our present results demonstrate that the sequences responsible for RA-induced activation of this gene are localized within the 0.4 kb of its 5'-flanking region and implicate RXR alpha involvement in this regulation. The active RA/RXR alpha responsive region is pinned down to two regulatory elements. Only in the presence of both elements full RA/RXR alpha inducibility is achieved, suggesting they act synergistically. These elements comprise two unique G-rich boxes, separated by 49 bp, that could be considered as a novel, atypical RA-response element. Here, for the first time, we have demonstrated interaction of RXR alpha and SOX3 control elements, suggesting that human SOX3 gene is a direct target for this retinoid receptor. Our data may help in providing new insight into complex regulatory networks involved in retinoic acid induced neural differentiation of NT2/D1 cells. The fine-detailed molecular and genetic dissection is required to uncover the role of SOX3 gene during vertebrate neurogenesis.




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