Molecular mechanisms mediating methylation-dependent silencing of ribosomal gene transcription

被引:195
作者
Santoro, R [1 ]
Grummt, I [1 ]
机构
[1] German Canc Res Ctr, Div Mol Biol & Cell 2, D-69120 Heidelberg, Germany
关键词
D O I
10.1016/S1097-2765(01)00317-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:719 / 725
页数:7
相关论文
共 17 条
[1]  
Akhmanova A, 2000, J CELL SCI, V113, P4463
[2]   Activation of SRF-regulated chromosomal templates by Rho-family GTPases requires a signal that also induces H4 hyperacetylation [J].
Alberts, AS ;
Geneste, O ;
Treisman, R .
CELL, 1998, 92 (04) :475-487
[3]   SHORT-RANGE DNA LOOPING BY THE XENOPUS HMG-BOX TRANSCRIPTION FACTOR, XUBF [J].
BAZETTJONES, DP ;
LEBLANC, B ;
HERFORT, M ;
MOSS, T .
SCIENCE, 1994, 264 (5162) :1134-1137
[4]   LOSS OF RDNA METHYLATION ACCOMPANIES THE ONSET OF RIBOSOMAL GENE ACTIVITY IN EARLY DEVELOPMENT OF X-LAEVIS [J].
BIRD, A ;
TAGGART, M ;
MACLEOD, D .
CELL, 1981, 26 (03) :381-390
[5]   Methylation-induced repression - Belts, braces, and chromatin [J].
Bird, AP ;
Wolffe, AP .
CELL, 1999, 99 (05) :451-454
[6]   Mosaic methylation of the repeat unit of the human ribosomal RNA genes [J].
Brock, GJR ;
Bird, A .
HUMAN MOLECULAR GENETICS, 1997, 6 (03) :451-456
[7]   REGULATION OF CYTOSINE METHYLATION IN RIBOSOMAL DNA AND NUCLEOLUS ORGANIZER EXPRESSION IN WHEAT [J].
FLAVELL, RB ;
ODELL, M ;
THOMPSON, WF .
JOURNAL OF MOLECULAR BIOLOGY, 1988, 204 (03) :523-534
[8]   Mutations in ATRX, encoding a SWI/SNF-like protein, cause diverse changes in the pattern of DNA methylation [J].
Gibbons, RJ ;
McDowell, TL ;
Raman, S ;
O'Rourke, DM ;
Garrick, D ;
Ayyub, H ;
Higgs, DR .
NATURE GENETICS, 2000, 24 (04) :368-371
[9]   EFFICIENT TRANSCRIPTION OF A PROTEIN-CODING GENE FROM THE RNA POLYMERASE-I PROMOTER IN TRANSFECTED CELLS [J].
GRUMMT, I ;
SKINNER, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (03) :722-726
[10]   Involvement of in situ conformation of ribosomal genes and selective distribution of upstream binding factor in rRNA transcription [J].
Junera, HR ;
Masson, C ;
Geraud, G ;
Suja, J ;
HernandezVerdun, D .
MOLECULAR BIOLOGY OF THE CELL, 1997, 8 (01) :145-156