|
| Status |
Public on Jun 07, 2018 |
| Title |
Higher-order inter-chromosomal hubs shape 3-dimensional genome organization in the nucleus |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Other
|
| Summary |
We develop Split-Pool Recognition of Interactions by Tag Extension (SPRITE), which enables genome-wide detection of higher-order interactions that occur simultaneously within the nucleus in a proximity-ligation independent manner. We generated SPRITE maps in two mammalian cell types – mouse embryonic stem cells (mES) and human lymphoblastoid cells (GM12878). We generated ~1.5 billion sequencing reads from each sample and recapitulate known genome structures identified by Hi-C, including chromosome territories, compartments, topologically associated domains, and loop structures, and identify that many of these occur within higher-order structures in the nucleus. Because SPRITE does not rely on proximity-ligation, we find that SPRITE identifies interactions that occur across larger spatial distances than can be observed by Hi-C. These long-range interactions include two major hubs of inter-chromosomal interactions. We extended SPRITE to enable simultaneous measurements of RNA and DNA interactions and observe ribosomal RNA interactions across specific regions on the genome that correspond to DNA organization around the nucleolus. We show that gene-dense regions that are highly transcribed by PolII organize around nuclear speckles and gene poor, and therefore transcriptionally inactive, regions that are centromere-proximal organize around the nucleolus. In addition to the regions that directly associate around these nuclear bodies, we find that a substantial fraction of the genome exhibits preferential spatial positioning in the nucleus relative to each of these nuclear bodies and that the spatial preferences identified by SPRITE are highly correlated with 3D distances measured by microscopy.
|
| |
|
| Overall design |
DNA SPRITE was used to study 3D genome organization in mouse ES cells and human lymphoblasts. RNA-DNA SPRITE was used to map RNA and DNA interactions simultaneously in mouse ES cells.
Heatmaps are included in tar archives at the foot of this record in addition to the cluster data. Please see the file SPRITE_readme_heatmaps.rtf for information on heatmap generation.
|
| |
|
| Contributor(s) |
Quinodoz S, Guttman M |
| Citation(s) |
29887377 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| U01 DA040612 |
Deciphering the function and mechanisms of lncRNA-mediated organization of nuclear compartments |
CALIFORNIA INSTITUTE OF TECHNOLOGY |
Mitchell Guttman |
| U01 HL130007 |
Novel tools to comprehensively map dynamic organization of RNA and DNA in higher-order nuclear structures within single cells |
CALIFORNIA INSTITUTE OF TECHNOLOGY |
Mitchell Guttman |
|
| |
| Submission date |
May 09, 2018 |
| Last update date |
Mar 27, 2019 |
| Contact name |
Sofia Agustina Quinodoz |
| Organization name |
Princeton University
|
| Department |
CBE
|
| Lab |
Brangwynne Laboratory
|
| Street address |
25 William St
|
| City |
Princeton |
| State/province |
NJ |
| ZIP/Postal code |
08540 |
| Country |
USA |
| |
|
| Platforms (4)
|
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (20)
|
|
| Relations |
| BioProject |
PRJNA472993 |
| SRA |
SRP148905 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE114242_RNA_DNA_combined_clusters.tar.gz |
2.8 Gb |
(ftp)(http) |
TAR |
| GSE114242_SPRITE_readme_heatmaps.rtf |
6.4 Kb |
(ftp)(http) |
RTF |
| GSE114242_human_combined_clusters.tar.gz |
6.7 Gb |
(ftp)(http) |
TAR |
| GSE114242_human_config.txt.gz |
3.1 Kb |
(ftp)(http) |
TXT |
| GSE114242_human_inter_1Mb.tar.gz |
251.2 Mb |
(ftp)(http) |
TAR |
| GSE114242_human_intra_1Mb.tar.gz |
1.9 Mb |
(ftp)(http) |
TAR |
| GSE114242_human_intra_250kb.tar.gz |
27.9 Mb |
(ftp)(http) |
TAR |
| GSE114242_human_intra_25kb.tar.gz |
2.1 Gb |
(ftp)(http) |
TAR |
| GSE114242_human_intra_50kb.tar.gz |
594.8 Mb |
(ftp)(http) |
TAR |
| GSE114242_mouse_combined_clusters.tar.gz |
6.1 Gb |
(ftp)(http) |
TAR |
| GSE114242_mouse_config.tar.gz |
6.2 Kb |
(ftp)(http) |
TAR |
| GSE114242_mouse_inter_1Mb.tar.gz |
196.9 Mb |
(ftp)(http) |
TAR |
| GSE114242_mouse_intra_100kb.tar.gz |
131.5 Mb |
(ftp)(http) |
TAR |
| GSE114242_mouse_intra_1Mb.tar.gz |
1.6 Mb |
(ftp)(http) |
TAR |
| GSE114242_mouse_intra_200kb.tar.gz |
35.2 Mb |
(ftp)(http) |
TAR |
| GSE114242_mouse_intra_20kb.tar.gz |
2.7 Gb |
(ftp)(http) |
TAR |
| GSE114242_mouse_intra_400kb.tar.gz |
9.4 Mb |
(ftp)(http) |
TAR |
| GSE114242_mouse_intra_40kb.tar.gz |
749.7 Mb |
(ftp)(http) |
TAR |
| GSE114242_rna_dna_config.txt.gz |
2.6 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
Less...
More...