Genome-wide analysis of Bkm sequences (GATA repeats): predominant association with sex chromosomes and potential role in higher order chromatin organization and function

Abstract

Our extensive analysis of GATA repeats in the prokaryotic and eukaryotic genomes, which have been completely sequenced so far, has revealed that GATA repeats are absent in prokaryotes and have been gradually accumulated in higher organisms during the course of evolution. In human, the Y-chromosome has the highest GATA repeat density, which predominantly exists in the Yq centromeric region. Generally, occurrence of repeats in the genomes decreases steadily as the length of the repeat increases. In contrast, we report, that the occurrence of GATA repeats increases as the length of the repeat increases from six tandem repeats onwards and peaks at (GATA)(10-12). This has not been observed with any other simple repeat. Distribution of (GATA)(10-12) along the chromosome and their close proximity to Matrix Associated Regions (GATA-MAR) suggests that it may be demarking chromatin domains for a coordinated expression of genes residing in these domains.

GATA simple sequence repeats function as enhancer blocker boundaries

“…The barrier assay we used is based on the fact that upon drug withdrawal, transgenes in the genome get silenced over a period of time by the gradual spread of nearby repressive/heterochromatic activity and that if the transgene is flanked by barrier elements that can block the spread of repressive activity, they can stay active for longer periods 27 . We found that although both GATA 10 and GE7 test fragmentcontaining transgenes were active to start with, none of them protected the reporter from getting silenced. GE7, however, showed a varying rate of silencing of the reporter gene in NIH3T3 cell line experiment, seen as high s.d.…”

“…Presence of many SSR-binding proteins [29][30][31] further strengthens the view that these repeats may have functional relevance. One of the major SSRs in vertebrates, the GATA tetranucleotide, has many unique features such as preferred higher occurrence of (GATA) [10][11][12] , greater abundance on the mammalian Y chromosome and close association with developmentally regulated genes 9,10 . We here show that these GATA elements function as enhancer blocker elements that can demarcate functional domains in the genome.…”

“…GATA repeats have also been found to be associated with genes that are expressed early during development while the GE-devoid region of Y chromosome contains genes that are expressed late during spermatogenesis. We also noticed a frequent association of matrix attachment region (MAR) potential sequences with the GATA repeats 10 . MAR DNA, by its association to the nuclear matrix, creates chromatin domains that are topologically constrained, which helps in regulating genes and organizing the genome in eukaryotes [11][12][13][14][15] .…”

“…Certain repetitive sequences have been implicated in chromatin-mediated transcriptional regulation, chromosome organization, imprinting, chromatin domain boundary function and complex nuclear features such as heterochromatin, telomeres and nucleolar organization [1][2][3][4][5][6][7][8] . SSRs, on the other hand, have not been directly implicated in such regulatory roles although this class of DNA has also accumulated in complex genomes, particularly in vertebrates 9,10 .…”

“…GATA repeat elements (GEs), which are highly abundant on the sex chromosomes of several organisms, have GATA [10][11][12] as the most abundant size of this repeat and are present almost exclusively in the intergenic regions 10 . GATA repeats have also been found to be associated with genes that are expressed early during development while the GE-devoid region of Y chromosome contains genes that are expressed late during spermatogenesis.…”