Clustered transposon insertion via formation of chromatin loops DOI Creative Commons
Roshan Prizak, Lennart Hilbert

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Фев. 16, 2022

Transposons, which are DNA sequences that can move to new positions in the genome, make up a large fraction of eukaryotic genomes and occur clusters. The insertion transposons into genome is hindered by compact folding chromatin, supposedly preventing aberrant or even pathogenic insertion. Chromatin can, however, be decompacted as consequence transposon insertion, leading increased accessibility and, consequence, further insertions. While these observations suggest positive feedback between chromatin unfolding how such might contribute clustered remains poorly understood. In this study, we analyze polymer models self-interacting domain unfolds increasing numbers inserted block self-interaction. On one hand, find that, if additional adjacently already transposons, changes from sharp globule-coil transition more gradual extension loops core folded. other adjacent emerges either when transposases excluded densely packed proceeds very quickly relation thermal equilibration configurations. We thus derive our model physical conditions for resulting spatial compartmentalization chromatin. An according role was recently suggested LINE-1 Alu repeats, clusters drive mesoscopic mammalian genome. Significance Statement A part composed repetitive sequences, so-called transposons. Transposons involved important processes, early embryonic development control over genes used cell. frequently clusters, where many similar sequence motifs grouped together. Recent studies result local favoring yet Our work simulates simplified region transposases, molecules insert Surprisingly, fast-acting favor formation distinct contain most providing potential explanation

Язык: Английский

Genomic features underlie the co-option of SVA transposons as cis-regulatory elements in human pluripotent stem cells DOI Open Access
Samantha M. Barnada, Andrew Isopi, Daniela Tejada-Martínez

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Янв. 10, 2022

Abstract Domestication of transposable elements (TEs) into functional cis-regulatory is a widespread phenomenon. However, the mechanisms behind why some TEs are co-opted as enhancers while others not underappreciated. SINE-VNTR-Alus (SVAs) youngest group transposons in human genome, where ∼3,700 copies annotated, nearly half which human-specific. Many studies indicate that SVAs among most frequently gene regulation, but underlying such processes have yet been thoroughly investigated. Here, we leveraged CRISPR-interference (CRISPRi), computational and genomics to elucidate genomic features underlie SVA domestication stem-cell regulation. We found ∼750 induced pluripotent stem cells. These significantly closer genes harbor more transcription factor binding sites than non-co-opted SVAs. show long DNA motif composed flanking YY1/2 OCT4 enriched these two factors bind consecutively on TE sequence. used CRISPRi epigenetically repress active cell-like NCCIT Epigenetic perturbation strongly attenuated YY1/OCT4 influenced neighboring expression. Ultimately, repression resulted ∼3,000 differentially expressed genes, 131 were nearest an annotated SVA. In summary, demonstrated modulate expression, uncovered location sequence composition contribute regulatory networks.

Язык: Английский

Процитировано

3

Clustered transposon insertion via formation of chromatin loops DOI Creative Commons
Roshan Prizak, Lennart Hilbert

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Фев. 16, 2022

Transposons, which are DNA sequences that can move to new positions in the genome, make up a large fraction of eukaryotic genomes and occur clusters. The insertion transposons into genome is hindered by compact folding chromatin, supposedly preventing aberrant or even pathogenic insertion. Chromatin can, however, be decompacted as consequence transposon insertion, leading increased accessibility and, consequence, further insertions. While these observations suggest positive feedback between chromatin unfolding how such might contribute clustered remains poorly understood. In this study, we analyze polymer models self-interacting domain unfolds increasing numbers inserted block self-interaction. On one hand, find that, if additional adjacently already transposons, changes from sharp globule-coil transition more gradual extension loops core folded. other adjacent emerges either when transposases excluded densely packed proceeds very quickly relation thermal equilibration configurations. We thus derive our model physical conditions for resulting spatial compartmentalization chromatin. An according role was recently suggested LINE-1 Alu repeats, clusters drive mesoscopic mammalian genome. Significance Statement A part composed repetitive sequences, so-called transposons. Transposons involved important processes, early embryonic development control over genes used cell. frequently clusters, where many similar sequence motifs grouped together. Recent studies result local favoring yet Our work simulates simplified region transposases, molecules insert Surprisingly, fast-acting favor formation distinct contain most providing potential explanation

Язык: Английский

Процитировано

1