Histone Methylation by NUE, a Novel Nuclear Effector of the Intracellular Pathogen Chlamydia trachomatis

PLoS Pathogens

Stéphanie Perrinet¹  Agathe Subtil¹  Meghan E. Pennini²  Alice Dautry-Varsat² 

[1] CNRS URA 2582, Paris, France;Institut Pasteur, Unité de Biologie des Interactions Cellulaires, Paris, France

关键词: Histones;    Chlamydia trachomatis;    Chlamydia infection;    Chlamydia;    Protein domains;    DNA-binding proteins;    DNA methylation;    Methyltransferases;   

DOI  :  10.1371/journal.ppat.1000995

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Sequence analysis of the genome of the strict intracellular pathogen Chlamydia trachomatis revealed the presence of a SET domain containing protein, proteins that primarily function as histone methyltransferases. In these studies, we demonstrated secretion of this protein via a type III secretion mechanism. During infection, the protein is translocated to the host cell nucleus and associates with chromatin. We therefore named the protein nuclear effector (NUE). Expression of NUE in mammalian cells by transfection reconstituted nuclear targeting and chromatin association. In vitro methylation assays confirmed NUE is a histone methyltransferase that targets histones H2B, H3 and H4 and itself (automethylation). Mutants deficient in automethylation demonstrated diminished activity towards histones suggesting automethylation functions to enhance enzymatic activity. Thus, NUE is secreted by Chlamydia, translocates to the host cell nucleus and has enzymatic activity towards eukaryotic substrates. This work is the first description of a bacterial effector that directly targets mammalian histones.

【 授权许可】

CC BY