Transcription of PRDM1, the master regulator for plasma cell differentiation, depends on an SP1/SP3/EGR-1 GC-box

The positive regulatory domain containing 1, encoded by the PRDM1 gene, is a transcriptional repressor considered as a master regulator that is required and sufficient for plasma cell differentiation. In the present study we have performed sequence analysis of the upstream region of the human PRDM1...

Full description

Saved in:
Bibliographic Details
Published in:European journal of immunology 2008-08, Vol.38 (8), p.2316-2324
Main Authors: Mora-López, Francisco, Pedreño-Horrillo, Nuria, Delgado-Pérez, Luis, Brieva, José A, Campos-Caro, Antonio
Format: Article
Language:English
Subjects:
5' Flanking Region
B cell differentiation
Base Sequence
Cell Differentiation
Cells, Cultured
Early Growth Response Protein 1 - physiology
Human
Humans
Ionomycin - pharmacology
Molecular Sequence Data
Positive Regulatory Domain I-Binding Factor 1
PRDM1
Promoter Regions, Genetic
Regulatory Elements, Transcriptional
Repressor Proteins - genetics
Sp1 Transcription Factor - physiology
Sp3 Transcription Factor - physiology
Tetradecanoylphorbol Acetate - pharmacology
Transcription factors
Transcription Initiation Site
Transcription, Genetic
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The positive regulatory domain containing 1, encoded by the PRDM1 gene, is a transcriptional repressor considered as a master regulator that is required and sufficient for plasma cell differentiation. In the present study we have performed sequence analysis of the upstream region of the human PRDM1 gene to detect the minimal promoter region necessary for PRDM1 gene transcription. This region comprises the region upstream of the initiation site, as well as the first exon. Collectively, deletion and mutation analysis in conjunction with luciferase reporter assays, EMSA and supershift assays identified a phylogenetically conserved GC-box as an essential element for PRDM1 expression. This GC-box element matches to a binding site for multiple transcription factors such as SP1 and SP3 isoforms as well as early growth response 1. Chromatin immunoprecipitation assays confirmed the in vivo binding capability of these factors to the human PRDM1 promoter. These studies together characterize for the first time the basal activity of the human PRDM1 promoter, through which several factors, including SP1, SP3 and early growth response 1, modulate its expression through a conserved GC-box.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.200737861