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| Status |
Public on Apr 14, 2020 |
| Title |
Global chromatin occupancy and epigenetic signature analysis reveal new insights into the function of GATA1 N-terminus in erythropoiesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
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| Summary |
Mutations in GATA1, which lead to expression of the GATA1s isoform that lacks the GATA1 N-terminus, are seen in patients with Diamond-Blackfan Anemia (DBA). In our efforts to better understand the connection between GATA1s and DBA, we comprehensively studied erythropoiesis in Gata1s mice. Defects in yolks sac and fetal liver hematopoiesis included impaired terminal maturation and reduced numbers of erythroid progenitors. RNA-sequencing revealed that both erythroid and megakaryocytic genes were altered by the loss of the N-terminus, including aberrant up-regulation of Gata2 and Runx1. Mass spectrometry studies demonstrated there was a global increase in H3K27 methylation in the erythroid progenitors. By contrast, chromatin biding assays revealed that, despite similar occupancy of GATA1 and GATA1s, there was a striking reduction of H3K27me3 at regulatory elements of the Gata2 and Runx1 genes. Consistent with the observation that overexpression of GATA2 has been reported to impair erythropoiesis, we found that haploinsufficiency of Gata2 rescued the erythroid defects of Gata1s fetuses. Together, our integrated genomic analysis of transcriptomic and epigenetic signatures reveals that, although Gata1s mice do not precisely model DBA, they provide novel insights into the role of the N-terminus of GATA1 in transcriptional regulation and red blood cell maturation.
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| Overall design |
Fetal liver cells from Gata1s embryos were stained with antibodies against CD71 and Ter119, CD71hiTer119neg/low population (R1/2) and CD71hiTer119hi (R3) population were sorted for analysis comparing with corresponding populations of fetal liver cells from wild type embryos.
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| Contributor(s) |
Ling T, Zou L, Ben-Haim N, Crispino JD |
| Citation(s) |
31409672 |
| |
| Submission date |
Apr 22, 2019 |
| Last update date |
Apr 14, 2020 |
| Contact name |
John Crispino |
| E-mail(s) |
zoul@northwestern.edu
|
| Organization name |
Northwestern University
|
| Street address |
300 Superior St
|
| City |
Chicago |
| ZIP/Postal code |
60201 |
| Country |
USA |
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| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (60)
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| Relations |
| BioProject |
PRJNA534276 |
| SRA |
SRP193466 |
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