RESEARCH ARTICLE
Gene Regulation at a Distance in the Epidermal Keratinocyte: The Paradigm of the PADI Gene Locus
Stephane Chavanas*, 1, 2, Veronique Adoue1, 3, Guy Serre1, Michel Simon*, 1
Article Information
Identifiers and Pagination:
Year: 2010Volume: 4
First Page: 21
Last Page: 26
Publisher ID: TODJ-4-21
DOI: 10.2174/1874372201004010021
Article History:
Received Date: 28/08/2009Revision Received Date: 09/11/2009
Acceptance Date: 10/12/2009
Electronic publication date: 23/4/2010
Collection year: 2010
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Long-range cis elements are critical regulators of gene transcription, particularly for paralogous genes clustered on a unique chromosomal region. Such are the five PADI genes in 1p35 36 encoding peptidylarginine deiminases. These enzymes catalyze deimination, or citrullination, a calcium-dependent post-translational modification of proteins which has been implicated in gene regulation and in the pathophysiology of multiple sclerosis and rheumatoid arthritis. The epidermis is an exciting model for understanding PADI gene regulation since only the genes PADI 1 3 are expressed in the epidermal keratinocytes, with increased expression levels in the most differentiated cells. Studies on PADI proximal promoters failed to explain such a specificity of expression. Here, we describe long-range regulatory elements identified as essential for the PADI3 specific expression in differentiated keratinocytes through the formation of a chromatin loop.