Baoxu Pang, Michael P. Snyder
The majority of the human genome does not encode proteins. Many of these noncoding regions contain important regulatory sequences that control gene expression. To date, most studies have focused on activators such as enhancers, but regions that repress gene expression—silencers—have not been systematically studied. We have developed a system that identifies silencer regions in a genome-wide fashion on the basis of silencer-mediated transcriptional repression of caspase 9. We found that silencers are widely distributed and may function in a tissue-specific fashion. These silencers harbor unique epigenetic signatures and are associated with specific transcription factors. Silencers also act at multiple genes, and at the level of chromosomal domains and long-range interactions. Deletion of silencer regions linked to the drug transporter genes ABCC2 and ABCG2 caused chemo-resistance. Overall, our study demonstrates that tissue-specific silencing is widespread throughout the human genome and likely contributes substantially to the regulation of gene expression and human biology.
Baoxu Pang, Michael P. Snyder. Systematic identification of silencers in human cells. 2020-02-24. https://doi.org/10.1038/s41588-020-0578-5
The same approximately 200-bp K562 FAIRE-enriched ReSE library was assayed after K562 cells were differentiated with PMA. AP20187-selected survivors were compared with PMA-treated untreated controls in two biological replicates, and the table contains the published significantly enriched silencer fragments.
The K562 FAIRE-enriched approximately 200-bp ReSE library was assayed in HepG2 cells. AP20187-selected survivors were compared with untreated controls in two biological replicates, and the table contains the published significantly enriched silencer fragments.
A pooled library of approximately 200-bp K562 FAIRE-enriched genomic fragments was integrated into K562 cells upstream of an EF-1α-FKBP-Casp9 reporter. AP20187-selected survivors were compared with untreated controls in two biological replicates, and the table contains the published significantly enriched silencer fragments.
Original supplemental and deposited inputs retained for this study. Download files individually or together as a ZIP; nested folders are preserved. Source reuse terms apply, and sequencing reads may be omitted.
Download all 7 files (ZIP)GSE108536_family.soft.gzGSE108536_HepG2_FDR_0.01.bed.gzGSE108536_K562_FDR_0.01.bed.gzGSE108536_K562_PMA_FDR_0.01.bed.gzSupplementary_Table_1_K562.xlsxSupplementary_Table_2_K562_PMA.xlsxSupplementary_Table_3_HepG2.xlsx