HeLa E-Box Binding Protein, HEB, Inhibits Promoter Activity of the Lysophosphatidic Acid Receptor Gene Lpar1 in Neocortical Neuroblast Cells
Nam-Ho Kim1,4, Ali Sadra1,4, Hee-Young Park1, Sung-Min Oh1, Jerold Chun2, Jeong Kyo Yoon3,*, and Sung-Oh Huh1,*
1Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Gangwon-do 24252, Korea, 2Sanford Burnham Prebys Medical Discovery Institute, CA 92037, USA, 3Soonchunhyang Institute of Medi-Bio Science, Soonchunhyang University, Choongcheongnam-do 31538, Korea, 4These authors contributed equally to this work.
Received October 2, 2018; Revised December 4, 2018; Accepted December 7, 2019.; Published online January 2, 2019.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit (http://creativecommons.org/licenses/by-nc-sa/3.0/).
ABSTRACT
Lysophosphatidic acid (LPA) is an endogenous lysophospholipid with signaling properties outside of the cell and it signals
through specific G protein-coupled receptors, known as LPA1-6. For one of its receptors, LPA1 (gene name Lpar1), details on the cis-acting elements for transcriptional control have not been defined. Using 5′RACE analysis, we report the identification of an alternative transcription start site of mouse Lpar1 and characterize approximately 3,500 bp of non-coding flanking sequence 5′ of mouse Lpar1 gene for promoter activity. Transient transfection of cells derived from mouse neocortical neuroblasts with constructs from the 5′ regions of mouse Lpar1 gene revealed the region between -248 to +225 serving as the basal promoter for Lpar1. This region also lacks a TATA box. For the region between -761 to -248, a negative regulatory element affected the basal expression of Lpar1. This region has three E-box sequences and mutagenesis of these E-boxes, followed by transient expression, demonstrated that two of the E-boxes act as negative modulators of Lpar1. One of these E-box sequences bound the HeLa Ebox binding protein (HEB), and modulation of HEB levels in the transfected cells regulated the transcription of the reporter gene. Based on our data, we propose that HEB may be required for a proper regulation of Lpar1 expression in the embryonic neocortical neuroblast cells and to affect its function in both normal brain development and disease settings. 
Keywords:
alternative splicing, HeLa E-box binding protein, lysophosphatidic acid receptor 1, transcription repressor


Current Issue

31 December 2018 Volume 41,
Number 12, pp. 993~1081

This Article


Cited By Articles
  • CrossRef (0)

Social Network Service
Services

Indexed in

  • Science Central
  • CrossMark