The chromatin remodeling complex NoRC and TTF-I cooperate in the regulation of the mammalian rRNA genes in vivo.
The transcription termination factor (TTF)-I is a multifunctional nucleolar protein that terminates ribosomal gene transcription, mediates replication fork arrest and regulates RNA polymerase I transcription on chromatin. TTF-I plays a dual role in rDNA regulation, being involved in both activation and silencing of rDNA transcription. The N-terminal part of TTF-I contains a negative regulatory domain (NRD) that inhibits DNA binding. Here we show that interactions between the NRD and the C-terminal part of TTF-I mask the DNA-binding domain of TTF-I. However, interaction with TIP5, a subunit of the nucleolar chromatin remodeling complex, NoRC, recovers DNA-binding activity. We have mapped the protein domains that mediate the interaction between TTF-I and TIP5. The association of TIP5 with the NRD facilitates DNA binding of TTF-I and leads to the recruitment of NoRC to the rDNA promoter. Thus, TTF-I and NoRC act in concert to silence rDNA transcription.
Németh
Attila
A
Adolf Butenandt Institut, Molekularbiologie, Ludwig-Maximilians-Universität München, Schillerstrasse 44, D-80336 München, Germany.
Strohner
Ralf
R
Grummt
Ingrid
I
Längst
Gernot
G
D000818:Animals; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D020868:Gene Silencing; D020459:Genes, rRNA; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D041681:NIH 3T3 Cells; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000378:metabolism; D012318:RNA Polymerase I / Q000037:antagonists & inhibitors; D014157:Transcription Factors; D014158:Transcription, Genetic
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D021122:Protein Subunits; C504003:TTF1 protein, human; D014157:Transcription Factors; C504004:Ttf1 protein, mouse; D004247:DNA; D012318:RNA Polymerase I