|
| Status |
Public on May 11, 2023 |
| Title |
Complementary Alu sequences mediate enhancer-promoter selectivity |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Other
Expression profiling by high throughput sequencing
|
| Summary |
Enhancers determine spatiotemporal gene expression programs by engaging with long-range promoters. However, it remains unknown how enhancers find their cognate promoters. We recently developed a RIC-seq technology to identify enhancer-promoter connectivity using pairwise interacting enhancer RNAs and promoter-derived noncoding RNAs in HeLa cells. Here, we apply this technology to generate high-confidence enhancer-promoter RNA interaction (EPRI) maps in six additional cell lines. Using these maps, we discover that 37.9% of the enhancer-promoter RNA interaction sites are overlapped with Alu sequences. These pairwise interacting Alu and non-Alu RNA sequences tend to be complementary and potentially form duplexes. Knockout of Alu elements compromises enhancer-promoter looping, whereas Alu insertion or CRISPR-dCasRx-mediated Alu tethering to unregulated promoter RNAs can create new loops to homologous enhancers. Importantly, mapping 535,404 noncoding risk variants back to the EPRI maps enabled us to construct variant-to-function maps for interpreting their molecular functions, including 15,318 deletions or insertions in 11,677 Alu elements that affect 6,497 protein-coding genes. We further demonstrate that polymorphic Alu insertion at PTK2 enhancer can promote tumorigenesis. Our study uncovers a principle for determining enhancer-promoter pairing specificity and provides a framework to link noncoding risk variants to their molecular functions.
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| |
|
| Overall design |
We applied RIC-seq technology to construct high-resolution enhancer-promoter RNA interaction maps in HeLa and additional six cell lines representing three distinct germ layers, and Chromatin-associated nascent RNA sequencing (ChromRNA-seq) to confirm the decreased transcription of SE351-linked genes after knocking down the corresponding eRNA.
|
| Web link |
http://www.nature.com/articles/s41586-023-06323-x
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| |
|
| Contributor(s) |
Liang L, Cao C, Ji L, Cai Z, Xue Y |
| Citation(s) |
37438529 |
| |
| Submission date |
Dec 05, 2021 |
| Last update date |
Aug 18, 2023 |
| Contact name |
Yuanchao Xue |
| E-mail(s) |
ycxue@ibp.ac.cn
|
| Organization name |
Chinese Academy of Sciences
|
| Department |
Institute of Biophysics
|
| Lab |
Key Laboratory of RNA Biology
|
| Street address |
Datun Road #15
|
| City |
Beijing |
| ZIP/Postal code |
100101 |
| Country |
China |
| |
|
| Platforms (3) |
|
| Samples (23)
|
|
| Relations |
| BioProject |
PRJNA786348 |
| SRA |
SRP349307 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE190214_EP_and_PP.GM12878.network.xlsx |
2.0 Mb |
(ftp)(http) |
XLSX |
| GSE190214_EP_and_PP.H1.network.xlsx |
463.3 Kb |
(ftp)(http) |
XLSX |
| GSE190214_EP_and_PP.HeLa.network.xlsx |
3.2 Mb |
(ftp)(http) |
XLSX |
| GSE190214_EP_and_PP.HepG2.network.xlsx |
345.2 Kb |
(ftp)(http) |
XLSX |
| GSE190214_EP_and_PP.IMR90.network.xlsx |
667.3 Kb |
(ftp)(http) |
XLSX |
| GSE190214_EP_and_PP.K562.network.xlsx |
451.5 Kb |
(ftp)(http) |
XLSX |
| GSE190214_EP_and_PP.hNPC.network.xlsx |
2.6 Mb |
(ftp)(http) |
XLSX |
| GSE190214_GM12878.Enhancer_Promoter.chimeric_fragment.bed.gz |
5.4 Mb |
(ftp)(http) |
BED |
| GSE190214_H1.Enhancer_Promoter.chimeric_fragment.bed.gz |
992.4 Kb |
(ftp)(http) |
BED |
| GSE190214_HeLa.Enhancer_Promoter.chimeric_fragment.bed.gz |
9.0 Mb |
(ftp)(http) |
BED |
| GSE190214_HepG2.Enhancer_Promoter.chimeric_fragment.bed.gz |
815.4 Kb |
(ftp)(http) |
BED |
| GSE190214_IMR90.Enhancer_Promoter.chimeric_fragment.bed.gz |
1.8 Mb |
(ftp)(http) |
BED |
| GSE190214_K562.Enhancer_Promoter.chimeric_fragment.bed.gz |
1.3 Mb |
(ftp)(http) |
BED |
| GSE190214_MEF.Enhancer_Promoter.chimeric_fragment.bed.gz |
1.2 Mb |
(ftp)(http) |
BED |
| GSE190214_RAW.tar |
793.1 Mb |
(http)(custom) |
TAR (of BIGWIG) |
| GSE190214_hNPC.Enhancer_Promoter.chimeric_fragment.bed.gz |
7.2 Mb |
(ftp)(http) |
BED |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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