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| Status |
Public on Jul 09, 2019 |
| Title |
Chromatin structure dynamics during human cardiomyocyte differention reveals a role of HERV-H in demarcating TAD boundaries. |
| Organisms |
Callithrix jacchus; Pan paniscus; Pan troglodytes; Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
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| Summary |
The three-dimensional chromatin architecture plays a critical role in the establishment of cell-type-specific gene regulatory networks in eukaryotic cells. How pluripotent stem cells (PSC) alter their chromatin architecture to direct cell fate specification remains to be elucidated. Here, using a human PSC cardiomyocyte differentiation model, we analyze the dynamic reorganization of chromatin structure and gene regulatory networks during key transitional stages of cardiomyocyte development. We show that many human PSC-specific topologically associating domains (TADs) are driven by active transcription of the primate-specific retroviruses HERVH. These HERVH are silenced at the earliest stages of differentiation , accompanied by loss of TAD borders and subsequent merging of cognate TADs during differentiation, which leads to repression of gene expression within these domains . In line with these findings, deletion of select HERVHs results in elimination of corresponding TAD boundaries in human PSCs. We further discovered developmental stage-specific chromatin loop interactions that predict target genes of cardiac-related trait/disease non-coding genetic variants. Overall, our results not only highlight a novel role for endogenous retroviruses in shaping species-specific PSC chromatin architecture during evolution but also provide a genomic blueprint for understanding the impact of non-coding variants in congenital and adult heart disease/traits.
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| Overall design |
hESCs are differentiated into cardiomyocyte. We used a transgenic H9 hESC line expressing a H2B-GFP fusion protein under control of the ventricular cardiomyocyte specific MYL2 promoter. We collected samples at six critical time points during differentiation: human embryonic stem cells (hESC) (Day 0), hESC mesodermal cells (Day 2), hESC-cardiac mesodermal cells (Day 5), hESC-cardiac progenitor cell (Day 7), hESC-primitive cardiomyocytes (Day 15) and hESC-ventricular cardiomyocytes (Day 80). We performed HiC, ATAC-seq, RNA-seq, and ChIP-seq for H3K27ac, H3K27me3, H3K4me1, H3K4me3, H3K9me3 and CTCF for every time point, each with two biological replicates. We also made CRISPR edited deletion at two HERV-H loci and performed RNA-seq and Hi-C, each with two replicates.
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| Contributor(s) |
Ren B, Chi N, Zhang Y, Preissl S, Destici E, Li T, Yang H, Grinstein J, Lee A, Chee S, Ye Z, Ma K, Tedeschi N, Kuan S, Vevers J, Evans S |
| Citation(s) |
31427791, 32111823, 36817700 |
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| Submission date |
Jul 10, 2018 |
| Last update date |
Oct 22, 2024 |
| Contact name |
Bing Ren |
| E-mail(s) |
biren@ucsd.edu
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| Organization name |
University of California, San Diego
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| Street address |
9500 Gilman Drive
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| City |
La Jolla |
| ZIP/Postal code |
92093 |
| Country |
USA |
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| Platforms (5)
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| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL23423 |
Illumina HiSeq 4000 (Pan troglodytes) |
| GPL26353 |
Illumina HiSeq 4000 (Pan paniscus) |
| GPL26566 |
Illumina HiSeq 4000 (Callithrix jacchus) |
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| Samples (115)
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| This SubSeries is part of SuperSeries: |
| GSE186958 |
Chromatin structure dynamics during human cardiomyocyte differention |
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| Relations |
| BioProject |
PRJNA480492 |
| SRA |
SRP152979 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE116862_RAW.tar |
248.6 Gb |
(http)(custom) |
TAR (of BW, HIC, RPKM, TXT) |
| GSE116862_bonobo.hic |
4.5 Gb |
(ftp)(http) |
HIC |
| GSE116862_chimp.mt.hic |
5.0 Gb |
(ftp)(http) |
HIC |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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