Open AccessDelivery of parasite Cdg7_Flc_0990 RNA transcript into intestinal epithelial cells during Cryptosporidium parvum infection suppresses host cell gene transcription through epigenetic mechanisms
Author(s) -
Wang Yang,
Gong AiYu,
Ma Shibin,
Chen Xiqiang,
StraussSoukup Juliane K.,
Chen XianMing
Publication year - 2017
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12760
Subject(s) - biology , epigenetics , gene , transcription (linguistics) , rna , gene expression , cryptosporidium parvum , microbiology and biotechnology , genetics , linguistics , philosophy
Summary Cryptosporidial infection causes dysregulated transcription of host genes key to intestinal epithelial homeostasis, but the underlying mechanisms remain obscure. Previous studies demonstrate that several Cryptosporidium parvum ( C . parvum ) RNA transcripts are selectively delivered into epithelial cells during host cell invasion and may modulate gene transcription in infected cells. We report here that C . parvum infection suppresses the transcription of LRP5 , SLC7A8 , and IL33 genes in infected intestinal epithelium. Trans‐suppression of these genes in infected host cells is associated with promoter enrichment of suppressive epigenetic markers (i.e., H3K9me3). Cdg7_FLc_0990, a C . parvum RNA that has previously demonstrated to be delivered into the nuclei of infected epithelial cells, is recruited to the promoter regions of LRP5 , SLC7A8 , and IL33 genes. Cdg7_FLc_0990 appears to be recruited to their promoter regions together with G9a, a histone methyltransferase for H3K9 methylation. The PR domain zinc finger protein 1, a G9a‐interacting protein, is required for the assembly of Cdg7_FLc_0990 to the G9a complex and gene‐specific enrichment of H3K9 methylation. Our data demonstrate that cryptosporidial infection induces epigenetic histone methylations in infected cells through nuclear transfer of parasite Cdg7_Flc_0990 RNA transcript, resulting in transcriptional suppression of the LRP5 , SLC7A8 , and IL33 genes.