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SRX13585226: GSM5769491: NCCIT_SVA_minusDoxy_Rep1; Homo sapiens; RNA-Seq
1 ILLUMINA (Illumina NovaSeq 6000) run: 17.8M spots, 3.6G bases, 1Gb downloads

External Id: GSM5769491_r1
Submitted by: Biochemistry and Molecular Biology, Thomas Jefferson University
Study: Specific genomic features underlie the co-option of SVA transposons as cis-regulatory elements in the human genome
show Abstracthide Abstract
Domestication of transposable elements (TEs) into functional cis-regulatory elements is a widespread phenomenon. However, why some TEs are co-opted as functional enhancers while others are not is underappreciated. SINE-Vntr-Alus (SVAs) are the youngest group of transposons in the human genome, where ~3,700 copies are annotated, nearly half of which are human-exclusive. Many studies indicated that the SVAs are among the most frequently co-opted TEs in human gene regulation, but the mechanisms underlying such process have not yet been thoroughly investigated. Here, we leveraged CRISPR-interference (CRISPRi), computational and functional genomics to elucidate the genomic features that underlie SVA domestication into human stem-cell gene regulation. We found that ~750 SVAs are co-opted as functional cis-regulatory elements in human induced Pluripotent Stem Cells. Co-opted SVAs are significantly closer to genes and harbor more transcription factor binding sites than the not co-opted ones. We show that a long DNA-motif composed of flanking YY1/2 and OCT4 binding sites is enriched in the co-opted SVAs, and that these two factors bind, as predicted, near each other on the TE sequence. Repression of all the ~750 co-opted SVAs by CRISPRi in a line with stem-like properties (NCCIT) led to loss of YY1/OCT4 binding and alteration of neighboring gene expression. Ultimately, SVA repression resulted in ~3,000 differentially expressed genes, 131 of which were the nearest gene to an annotated SVA. In summary, we demonstrated that SVAs contribute significantly to human gene regulation, and that both genomic location and sequence composition contribute to SVA domestication in the gene regulatory networks. Overall design: Using stem-like NCCIT cells to compare genomic consequences and gene regulation of repressing SVA transposons using CRISPR-interference
Sample: NCCIT_SVA_minusDoxy_Rep1
SAMN24592013 • SRS11475199 • All experiments • All runs
Organism: Homo sapiens
Library:
Name: GSM5769491
Instrument: Illumina NovaSeq 6000
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: PAIRED
Construction protocol: Cells were lysed in Tri-reagent (Zymo research) and total RNA was extracted using Quick-RNA Miniprep kit (Zymo research). RNA libraries were prepared using NEBNext® Poly(A) mRNA Magnetic Isolation Module, NEBNext® UltraTM II Directional RNA Library Prep Kit for Illumina® and NEBNext® UltraTM II DNA Library Prep Kit for Illumina® according to the manufacturer's instructions (New England Biolabs). 1 μg of total RNA input was used for each library
Runs: 1 run, 17.8M spots, 3.6G bases, 1Gb
Run# of Spots# of BasesSizePublished
SRR1741357917,849,0393.6G1Gb2022-01-04

ID:
18874139

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