Chromatin-specific regulation of mammalian rDNA transcription by clustered TTF-I binding sites.
Enhancers and promoters often contain multiple binding sites for the same transcription factor, suggesting that homotypic clustering of binding sites may serve a role in transcription regulation. Here we show that clustering of binding sites for the transcription termination factor TTF-I downstream of the pre-rRNA coding region specifies transcription termination, increases the efficiency of transcription initiation and affects the three-dimensional structure of rRNA genes. On chromatin templates, but not on free rDNA, clustered binding sites promote cooperative binding of TTF-I, loading TTF-I to the downstream terminators before it binds to the rDNA promoter. Interaction of TTF-I with target sites upstream and downstream of the rDNA transcription unit connects these distal DNA elements by forming a chromatin loop between the rDNA promoter and the terminators. The results imply that clustered binding sites increase the binding affinity of transcription factors in chromatin, thus influencing the timing and strength of DNA-dependent processes.
Biochemistry Centre Regensburg (BCR), University of Regensburg, Regensburg, Germany.
Sarah D
SD
Diermeier
Attila
A
Németh
Michael
M
Rehli
Ingrid
I
Grummt
Gernot
G
Längst
D000818:Animals; D001665:Binding Sites / Q000235:genetics*; D016466:CHO Cells; D002843:Chromatin / Q000235:genetics; D003412:Cricetulus; D004275:DNA, Ribosomal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D051379:Mice; D009707:Nucleosomes / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D012322:RNA Precursors / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D002843:Chromatin; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D009707:Nucleosomes; D012322:RNA Precursors; D014157:Transcription Factors; C504004:Ttf1 protein, mouse