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Synthetic reversed sequences reveal default genomic states

ABSTRACT: Synthetic reversed sequences reveal default genomic states

PROVIDER: PRJNA1060710 | ENA |

REPOSITORIES: ENA

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Synthetic reversed sequences reveal default genomic states

Project description:Pervasive transcriptional activity is observed across diverse species. The genomes of extant organisms have undergone billions of years of evolution, making it unclear whether these genomic activities represent effects of selection or ‘noise’1,2,3,4. Characterizing default genome states could help understand whether pervasive transcriptional activity has biological meaning. Here we addressed this question by introducing a synthetic 101-kb locus into the genomes of Saccharomyces cerevisiae and Mus musculus and characterizing genomic activity. The locus was designed by reversing but not complementing human HPRT1, including its flanking regions, thus retaining basic features of the natural sequence but ablating evolved coding or regulatory information. We observed widespread activity of both reversed and native HPRT1 loci in yeast, despite the lack of evolved yeast promoters. By contrast, the reversed locus displayed no activity at all in mouse embryonic stem cells, and instead exhibited repressive chromatin signatures. The repressive signature was alleviated in a locus variant lacking CpG dinucleotides; nevertheless, this variant was also transcriptionally inactive. These results show that synthetic genomic sequences that lack coding information are active in yeast, but inactive in mouse embryonic stem cells, consistent with a major difference in ‘default genomic states’ between these two divergent eukaryotic cell types, with implications for understanding pervasive transcription, horizontal transfer of genetic information and the birth of new genes.

2024-01-16 | GSE252482 | GEO

Synthetic reversed sequences reveal default genomic states [Yeast_ChIPseq]

Project description:Understanding default genome states would help interpret whether pervasive transcriptional activity has biological meaning. The genomes of extant organism have undergone billions of years of evolution, making it unclear whether observed genomic activities represent the effects of selection or “noise”. We addressed this question by introducing a novel 101-kb locus into the genomes of S. cerevisiae and M. musculus, and characterizing genomic activity. The locus was designed by reversing but not complementing human HPRT1, including substantial flank-ing regions, retaining basic sequence features but ablating evolved coding or regulatory infor-mation. We observed widespread activity of both reversed and native HPRT1 loci in yeast, de-spite the lack of evolved yeast promoters. In contrast, the reversed locus displayed no activity at all in mouse embryonic stem cells, instead showing repressive chromatin signatures. The re-pressive signature was alleviated in a locus variant lacking CpG dinucleotides; nevertheless this variant too was transcriptionally inactive. These results show that novel genomic sequences lacking coding information are active in yeast, but inactive in mouse embryonic stem cells, con-sistent with a major difference in “default genomic states” between these two divergent eukary-otic cell types, with implications for understanding pervasive transcription, horizontal transfer of genetic information, and new gene birth.

2024-01-16 | GSE252472 | GEO