Potential genetic functions of tandem repeated DNA sequence blocks in the human genome are based on a highly conserved ?chromatin folding code?

Abstract

This review is based on a thorough description of the structure and sequence organization of tandemly organized repetitive DNA sequence families in the human genome; it is aimed at revealing the locus-specific sequence organization of tandemly repetitive sequence structures as a highly conserved DNA sequence code. These repetitive so-called "super-structures" or "higher-order" structures are able to attract specific nuclear proteins. I shall define this code therefore as a "chromatin folding code". Since locus-specific superstructures of tandemly repetitive sequence units are present not only in the chromosome centromere or telomere region but also on the arms of the chromosomes, I assume that their chromatin folding code may contribute to, or even organize, the folding pathway of the chromatin chain in the nucleus. The "chromatin folding code" is based on its specific "chromatin code", which describes the sequence dependence of the helical pathway of the DNA primary sequence (i.e., secondary structure) entrapping the histone octamers in preferential positions. There is no periodicity in the distribution of the nucleosomes along the DNA chain. The folding pathway of the nucleosomal chromatin chain is however still flexible and determined by e.g., the length of the DNA chain between the nucleosomes. The fixation and stabilization of the chromatin chain in the space of the nucleus (i.e., its "functional state") may be mediated by additionally unique DNA protein interactions that are dictated by the "chromatin folding code". The unique DNA-protein interactions around the centromeres of human chromosomes are revealed for example by their "C-banding". I wish to stress that it is not my aim to relate each block of repetitive DNA sequences to a specific "chromatin folding code", but I shall demonstrate that there is an inherent potential for tandem repeated sequence units to develop a locus-specific repetitive higher order structure; this potential may create a specific chromatin folding code whenever a selection force exists at the position of this repetitive DNA structure in the genome.

Atypical deletions suggest five 22q11.2 critical regions related to the DiGeorge/velo-cardio-facial syndrome

“…33,34 Whether these transcripts affect the chromatin structure, which in turn modifies the transcriptional activity of DGS/VCFS genes, remains to be determined. 35 An alternative possibility is that the DGS/CVFS phenotype results from alteration of the 'chromatin folding code' mediated by the deletion of low-copy DNA repeats within 36 Interestingly, a recent report has shown that chromosome breakpoints in DGS/VCFS patients occur within low-copy DNA repeats (LCR22s), 37 which overlap the five intervals described here. Another contribution to the understanding of DGS/VCFS molecular pathogenesis could be the engineering of mice carrying deletions mimicking the five DGS/VCFS intervals.…”

Polymorphisms in the FcεRIβ Promoter Region Affecting Transcription Activity: A Possible Promoter-Dependent Mechanism for Association between FcεRIβ and Atopy

“…2), which has a high potential to form the Z-DNA structure (23,24). The structural transition from a righthanded B-DNA conformation to a left-handed Z-DNA conformation has been shown to regulate gene transcription (25,26). It should also be noted that SNPs altering gene expression and those associated with diseases are often found in the CA repeat sequences (27)(28)(29).…”

Escherichia coli DNA polymerase IV contributes to spontaneous mutagenesis at coding sequences but not microsatellite alleles

“…Microsatellite sequences of 1-5 nucleotides per unit repeat are found throughout the human genome [1][2][3][4][5][6][7][8]. Microsatellite sequences are often hotspots for mutation, and an increase in mutagenesis is observed as the length of the repeated sequence increases [9,10].…”