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Transcriptional silencing of human Alu sequences and inhibition of protein binding in the box B regulatory elements by 5′‐CG‐3′ methylation
Author(s) -
Kochanek Stefan,
Renz Doris,
Doerfler Walter
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00068-k
Subject(s) - methylation , biology , microbiology and biotechnology , transcription (linguistics) , dna methylation , epigenetics of physical exercise , alu element , rna polymerase iii , rna polymerase ii , promoter , rna polymerase , rna , genetics , gene , gene expression , human genome , linguistics , philosophy , genome
In earlier work, we demonstrated that 5′‐CG‐3′ methylation inhibits the transcriptional activity of human Alu elements associated with the α 1 ‐globin and the angiogenin genes in a cell‐free transcription system from HeLa nuclear extracts. These studies have been extended to different Alu sequences and to investigations on the mechanism involved in transcriptional silencing by methylation. By comparing the results of DNase I and dimethyl sulfate (DMS) in vitro footprinting on a consensus sequence in the RNA polymerase III promoter control B region between the unmethylated and the 5′‐CG‐3′ methylated B box, evidence has been adduced for effects of 5′‐CG‐3′ methylation on the interaction of specific nuclear proteins with DNA sequences in the B control region of the Alu elements. These results are consistent with the interpretation that the 5′‐CG‐3′ methylation interferes with the binding of proteins that are essential for the function of the B control region in these RNA polymerase III‐transcribed elements, and that promoter methylation thus inhibits transcription.