TY - JOUR
T1 - Delivery of parasite Cdg7_Flc_0990 RNA transcript into intestinal epithelial cells during Cryptosporidium parvum infection suppresses host cell gene transcription through epigenetic mechanisms
AU - Wang, Yang
AU - Gong, Ai Yu
AU - Ma, Shibin
AU - Chen, Xiqiang
AU - Strauss-Soukup, Juliane K.
AU - Chen, Xian Ming
N1 - Funding Information:
We thank Drs. Min Li, Yan Li, Xin‐Tian Zhang, and Zhenping Ming for helpful and stimulating discussions, Dr. Yongyue Qi for his assistance with statistical analysis, and Barbara L. Bittner for her assistance in writing the manuscript. This work was supported by funding from the National Institutes of Health (AI116323 to X. M. C.) and the Nebraska Stem Cell Research Program (LB606 to X. M. C.), and by revenue from Nebraska's excise tax on cigarettes awarded to Creighton University through the Nebraska Department of Health and Human Services (DHHS; LB595 to X. M. C.). The project described was also supported by Grant G20RR024001 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the State of Nebraska, DHHS, the National Center for Research Resources, or the National Institutes of Health.
Funding Information:
This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health under the Assurance of Compliance Number A3348‐01. All animal experiments were done in accordance with procedures (protocol number #0959) approved by the Institutional Animal Care and Use Committee of Creighton University.
Publisher Copyright:
© 2017 John Wiley & Sons Ltd
PY - 2017/11
Y1 - 2017/11
N2 - 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.
AB - 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.
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U2 - 10.1111/cmi.12760
DO - 10.1111/cmi.12760
M3 - Article
C2 - 28655069
AN - SCOPUS:85023614535
VL - 19
JO - Cellular Microbiology
JF - Cellular Microbiology
SN - 1462-5814
IS - 11
M1 - e12760
ER -