The insulator protein CTCF represses transcription on binding to the (gt)(22)(ga)(15) microsatellite in intron 2 of the HLA-DRB1(*)0401 gene.

The insulator and transcription factor CTCF is a highly conserved 11 zinc finger protein possessing multiple specifities in DNA sequence recognition. CTCF regulates transcription of several genes, like the human oncogene c-myc or the chicken lysozyme gene by binding extremely divergent DNA sequences with different sets of its 11 zinc fingers. Recently, an insulator function was demonstrated for several CTCF binding elements. Here we show that CTCF binds to the (gt)(22)(ga)(15) microsatellite repeat A9 in intron 2 of the HLA-DRB1(*)0401 gene. Reporter gene activity is repressed by the A9 element. This repression is dependent on coexpressed CTCF and is even stronger compared with the CTCF binding site F1 of the chicken lysozyme gene, for which a silencer activity has been shown. This is the first report suggesting a function for microsatellite sequences in regulating specific gene expression.