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
1 CNRS-University of Toulouse, UMR5165, Toulouse, France
2 INSERM U563, Purpan University Hospital, Toulouse, France
3 Departments of Human Genetics and Medical Genetics, McGill University, Montreal, Canada


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Creative Commons License
© 2010 Chavanas et al.

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.

* Address correspondence to these authors at the CNRS-University of Toulouse, UMR5165, CHU Purpan, Place du Dr. Balvac, TSA40031, 31059, Toulouse, Cedex 9, France; Te􀁏: 33 5 6115 8427; Fax: 33 5 61499036; E-mails:stephane.chavanas@inserm.fr, michel.simon@udear.cnrs.fr


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.

Keywords: Gene expression, long-range transcriptional regulation, post-translational modification, epidermis.