Downregulation of Gene Expression by Alpha Satellite Transcripts

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Abstract
Satellite DNAs are highly abundant sequences which build functional centromere and pericentromeric heterochromatin in many eukaryotes. Apart from this structural role, their involvement in gene expression modulation has been demonstrated, although the detailed molecular mechanism is still missing. Here, using major human alpha satellite as a model system, we investigate the role of satellite transcripts in gene expression regulation. We generated cell lines with forced, exogenous overexpression of alpha satellite RNA and followed the expression levels of genes containg alpha satellite repeats within introns. Our results reveal a positive correlation between exogenous alpha satellite expression and the downregulation of alpha-associated genes, strongly suggesting that alpha satellite RNA affects their transcription. Notably, the elevated levels of exogenous alpha satellite RNA did not affect histone modifications characteristic of pericentromeric heterochromatin (e.g. H3K9me3 or H3K18Ac) or euchromatin (e.g. H3K4me2) at intronic alpha satellite loci. We propose that alpha satellite RNA directly interacts with homologous DNA at dispersed intronic satellite loci by forming RNA-DNA hybrid structures, which may affects chromatin structure and transcriptional activity. The results demostrate that alpha satellite RNA is not only involved in centromere and heterochromatin assembly but, as shown here for the first time, also plays a role in modulating the expression of alpha-associated genes.

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