H-DNA can act as a transcriptional insulator

The polypurine/polypyrimidine DNA stretches with repetitive sequences (H palindromes) can adopt triplex-mediated folded structures called H-DNA. H palindromes are more represented than expected for a random distribution of bases in eucaryotic genomes, suggesting that they could ensure some biological function. Most studies have focused attention on their possible involvement in the control of transcription because of their particularly high frequency in the 5'-flanking sequences of genes. Using the (5'-TTCCC-3')n sequence present in the upstream region of several genes, this work concludes to a novel potentiality of H palindromes: The strong ability to disrupt the cooperation between proximal elements initiating transcription and distal elements enhancing transcription over a long distance. We present three structural features of the TTCCC repeat likely to explain such an activity: (1) the visualization by electron microscopy showing that a long H palindrome spontaneously forms higher order tertiary structures; (2) the fact that this structure is a target for specific nuclear proteins displaying an affinity for single-stranded polypyrimidines; and (3) the preferential localization of the genomic TTCCC repetitive sequences at the level of chromosomal matrix attachment regions (MARs). We propose that H-DNA can insulate some genetic loci from influences of their chromosomal environment, and belongs to a subclass of genomic matrix attachment regions.