Molecular Mechanisms Mediating Methylation-Dependent Silencing of Ribosomal Gene Transcription
Molecular CellPublished 1 September 2001Open access
Raffaella Santoro, Ingrid Grummt
Citations246
SJR quartileQ1
SJR score9.05
SNIP2.89
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TL;DR
Ch chromatin immunoprecipitation assays demonstrate that methylation of the cytosine at -133 inhibits binding of the transcription factor UBF to nucleosomal rDNA, thereby preventing initiation complex formation and methylation may be a mechanism to inactivate rDNA genes and propagate transcriptional silencing through cell division.
Abstract
Epigenetic control mechanisms silence about half of ribosomal RNA genes (rDNA) in metabolically active cells. In the mouse, 40% of rDNA repeats are methylated and can be activated by 5-azacytidine treatment. In exploring the effect of methylation on rDNA transcription, we found that methylation of a single CpG dinucleotide within the upstream control element of the rDNA promoter (at -133) abrogates rDNA transcription both in transfection experiments and in in vitro assays using chromatin templates. Chromatin immunoprecipitation assays demonstrate that methylation of the cytosine at -133 inhibits binding of the transcription factor UBF to nucleosomal rDNA, thereby preventing initiation complex formation. Thus, methylation may be a mechanism to inactivate rDNA genes and propagate transcriptional silencing through cell division.
Keywords
Biochemistry, Genetics and Molecular Biology
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