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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
The antisense strand of small interfering RNAs directs histone methylation and transcriptional gene silencing in human cells
RNA, Volume 12, No. 2, Year 2006
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Description
To determine mechanistically how siRNAs mediate transcriptional gene silencing (TGS) in human cells, we have measured histone methylation at targeted promoters, the dependency on active transcription, and whether or not both strands of the siRNA are required for siRNA-mediated TGS. We report here that siRNA treatment increases both H3K9 and H3K27 methylation of the targeted EF1A promoter and that this increase is dependent on nuclear specific delivery of the siRNA. We also find that TGS can be directed by the antisense strand alone, and requires active transcription by RNA polymerase II in human cells as evidenced by sensitivity to α-amanatin. The observation of antisense strand-specific siRNA-mediated TGS of EF1A was substantiated by targeting the U3 region of the HIV-1 LTR/promoter. Furthermore, we show that the antisense strand of siRNA EF52 associates with the transiently expressed Flag-tagged DNMT3A, the targeted EF1A promoter, and trimethylated H3K27. The observations reported here implicate a functional link between siRNA-mediated targeting of genomic regions (promoters), RNA Pol II function, histone methylation, and DNMT3A and support a paradigm in which the antisense strands of siRNAs alone can direct sequence-specific transcriptional gene silencing in human cells. Published by Cold Spring Harbor Laboratory Press. Copyright © 2006 RNA Society.
Authors & Co-Authors
Weinberg, Marc S.
South Africa, Johannesburg
School of Clinical Medicine
Villeneuve, Louisa M.
United States, Duarte
City of Hope National Med Center
Ehsani, Ali
United States, Duarte
City of Hope National Med Center
Amarzguioui, Mohammed
United States, Duarte
City of Hope National Med Center
Aagaard, Lars
United States, Duarte
City of Hope National Med Center
Chen, Zhao Xia
United States, Duarte
City of Hope National Med Center
Riggs, Arthur D.
United States, Duarte
City of Hope National Med Center
Rossi, John J.
United States, Duarte
City of Hope National Med Center
Morris, Kevin V.
United States, San Diego
Scripps Research Institute
Statistics
Citations: 295
Authors: 9
Affiliations: 3
Identifiers
Doi:
10.1261/rna.2235106
ISSN:
13558382
e-ISSN:
14699001
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases