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Status |
Public on Oct 31, 2018 |
Title |
Loss of H3K9me3 heterochromatin at protein coding genes enables developmental lineage specification (RNA-Seq) |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Domains of transcriptionally repressed heterochromatin, decorated by histone 3 lysine 9 trimethylation (H3K9me3), are reduced in embryonic stem cells compared to fully differentiated cells. However, the establishment and dynamics of closed regions of chromatin at protein coding genes, in natural embryologic development, has not been described. We developed a novel, antibody-independent method to isolate and map compacted heterochromatin from low cell number samples. Unexpectedly, we uncovered extensive high levels of H3K9me3-decorated, compacted heterochromatin at protein coding genes in early, uncommitted cells in the three germ layers, undergoing profound rearrangements and reduction upon differentiation, concomitant with cell type-specific gene expression. Perturbation of the three H3K9me3-related methyltransferases revealed that H3K9me3 heterochromatin is required to maintain cell lineage fidelity. We propose a key role for chromatin-based restriction of gene activity via H3K9me3 during embryologic development
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Overall design |
Study is an analysis by RNA-seq of pancreatic and hepatic development, with a trajectory including definitive endoderm (e8.25 ENDM1+), hepatic precursor (e10.5 Liv2+), and adult hepatocytes as well as pancreatic precursor (e10.5 PDX1+), immature beta cells (e18.5 INS-RFP+) and mature beta cells (8 week INS-RFP+); Ctrl and TKO 1 month old livers; each stage has two replicates; ENDM1+ is treated for some analyses as a baseline condition
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Contributor(s) |
Nicetto D, Donahue G, Jain T, Peng T, Sidoli S, Sheng L, Montavon T, Becker JS, Grindheim JM, Blahnik K, Garcia BA, Tan K, Bonasio R, Jenuwein T, Zaret KS |
Citation(s) |
30606806 |
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Submission date |
May 08, 2018 |
Last update date |
Mar 25, 2019 |
Contact name |
dario nicetto |
Organization name |
University of Pennsylvania
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Department |
Cell and Developmental Biology
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Lab |
Zaret Lab
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Street address |
3400 Civic Center Blvd
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City |
Philadelphia |
State/province |
PA |
ZIP/Postal code |
19104 |
Country |
USA |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (16)
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This SubSeries is part of SuperSeries: |
GSE114198 |
Loss of H3K9me3 heterochromatin at protein coding genes enables developmental lineage specification |
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Relations |
BioProject |
PRJNA470536 |
SRA |
SRP145005 |
Supplementary file |
Size |
Download |
File type/resource |
GSE114195_1619-1mo-triple-mut_S7.bw |
79.0 Mb |
(ftp)(http) |
BW |
GSE114195_1620-1mo-triple-mut_S4.bw |
75.4 Mb |
(ftp)(http) |
BW |
GSE114195_1630-1mo-ctrl_S10.bw |
69.6 Mb |
(ftp)(http) |
BW |
GSE114195_1647-1mo-ctrl_S8.bw |
42.2 Mb |
(ftp)(http) |
BW |
GSE114195_8w_INS-RFP_RNA_R1R2.bw |
27.0 Mb |
(ftp)(http) |
BW |
GSE114195_ENDM1-rep1_S6.bw |
8.9 Mb |
(ftp)(http) |
BW |
GSE114195_ENDM1.RNA.R2.bw |
47.8 Mb |
(ftp)(http) |
BW |
GSE114195_HEP_RNA_R1R2.bw |
68.6 Mb |
(ftp)(http) |
BW |
GSE114195_LIV2_RNA_R1R2.bw |
53.8 Mb |
(ftp)(http) |
BW |
GSE114195_PDX1_RNA_R1R2.bw |
41.1 Mb |
(ftp)(http) |
BW |
GSE114195_e18.5_INS-RFP_RNA_R1R2.bw |
39.4 Mb |
(ftp)(http) |
BW |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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