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Nucleic Acids Research Advance Access published online on December 15, 2006
Nucleic Acids Research, doi:10.1093/nar/gkl980
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© 2006 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Expression of RAB4B, a protein governing endocytic recycling, is co-regulated with MHC class II genes

Michal Krawczyk, Elisa Leimgruber, Queralt Seguín-Estévez, Isabelle Dunand-Sauthier, Emmanuèle Barras and Walter Reith*

Department of Pathology and Immunology, University of Geneva Medical School, CMU, 1 rue Michel-Servet, CH-1211 Geneva, Switzerland

*To whom correspondence should be addressed. Tel: +41 22 379 56 66; Fax: +41 22 379 57 46; Email: walter.reith{at}medecine.unige.ch

Received October 2, 2006. Revised October 26, 2006. Accepted October 26, 2006.

The small GTPase RAB4 regulates endocytic recycling, a process that contributes to Major Histocompatibility Complex (MHC)-mediated antigen presentation by specialized antigen presenting cells (APC) of the immune system. The gene encoding the RAB4B isoform of RAB4 was singled out by two complementary genome-wide screens. One of these consisted of a computer scan to identify genes containing characteristic MHC class II-related regulatory sequences. The second was the use of chromatin immunoprecipitation coupled to microarrays (ChIP-on-chip) to identify novel targets of a transcriptional co-activator called the MHC class II transactivator (CIITA). We show that the RAB4B gene is regulated by a typical MHC class II-like enhancer that is controlled directly by both CIITA and the multiprotein transcription factor complex known as the MHC class II enhanceosome. RAB4B expression is thus activated by the same regulatory machinery that is known to be essential for the expression of MHC class II genes. This molecular link between the transcriptional activation of RAB4B and MHC class II genes implies that APC boost their antigen presentation capacity by increasing RAB4-mediated endocytic recycling.

Present address: Michal Krawczyk, Regulatory Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA


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