Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

The antisense strand of small interfering RNAs directs histone methylation and transcriptional gene silencing in human cells

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Weinberg, Marc
  • Villeneuve, L. M.
  • Ehsani, A.
  • Amarzguioui, M.
  • Aagaard, L.
  • Chen, Z. X.
  • Riggs, A. D.
  • Rossi, J. J.
  • Morris, Kevin

publication date

  • February 2006

journal

  • RNA-a Publication of the RNA Society  Journal

abstract

  • 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 alpha-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.

subject areas

  • Amanitins
  • Base Sequence
  • Cells, Cultured
  • DNA (Cytosine-5-)-Methyltransferase
  • HIV Long Terminal Repeat
  • Histones
  • Humans
  • Methylation
  • Molecular Sequence Data
  • Nuclear Proteins
  • Nucleic Acid Synthesis Inhibitors
  • Promoter Regions, Genetic
  • RNA Interference
  • RNA Polymerase II
  • RNA, Antisense
  • RNA, Small Interfering
  • Transcription Factors
scroll to property group menus

Research

keywords

  • HIV-1
  • RNAi
  • histone methylation
  • promoter targeting
  • siRNA
  • siRNA mediated TGS
  • transcriptional gene silencing (TGS)
scroll to property group menus

Identity

PubMed Central ID

  • PMC1370905

International Standard Serial Number (ISSN)

  • 1355-8382

Digital Object Identifier (DOI)

  • 10.1261/rna.2235106

PubMed ID

  • 16373483
scroll to property group menus

Additional Document Info

start page

  • 256

end page

  • 262

volume

  • 12

issue

  • 2

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support