Maintenance of a constitutive heterochromatin domain in vertebrates by a Dicer-dependent mechanism.
The 16 kilobase (kb) heterochromatin domain between the chicken beta-globin locus and the folate receptor gene is used here to study the roles of RNA-dependent mechanisms and histone modifications in the maintenance of a constitutive heterochromatic structure. Inhibition of histone deacetylase (HDAC) activity is shown to both increase intergenic transcription and render the heterochromatin more accessible to MspI digestion. We show that short interfering RNA (siRNA)-mediated downregulation of the enzyme Dicer has similar effects: histone acetylation is increased, transcript levels rise and the compact chromatin structure becomes more accessible to restriction endonucleases. We also show that the chicken Argonaute 2 homologue binds the 16 kb region in a Dicer-dependent manner and is necessary for a condensed chromatin structure. Heterochromatic domains of this kind, which are widely distributed in vertebrate genomes, thus seem to be maintained in their condensed form by highly conserved mechanisms.
Giles
Keith E
KE
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0540, USA.
Ghirlando
Rodolfo
R
Felsenfeld
Gary
G
D000107:Acetylation; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D002645:Chickens; D047369:Chromatin Immunoprecipitation; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D058973:Folate Receptors, GPI-Anchored; D006570:Heterochromatin / Q000235:genetics* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D019901:Locus Control Region; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043244:Ribonuclease III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D055544:beta-Globins / Q000235:genetics*
D002352:Carrier Proteins; D015852:Eukaryotic Initiation Factor-2; D058973:Folate Receptors, GPI-Anchored; D006570:Heterochromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055544:beta-Globins; D043244:Ribonuclease III; D006655:Histone Deacetylases