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| Status |
Public on Jul 11, 2016 |
| Title |
NF-E2, FLI1 and RUNX1 collaborate at areas of dynamic chromatin to activate transcription in mature mouse megakaryocytes |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Mutations in mouse and human Nfe2, Fli1 and Runx1 cause thrombocytopenia. We applied genome- wide chromatin dynamics and ChIP-seq to determine these transcription factors’ (TFs) activities in terminal megakaryocyte (MK) maturation. Enhancers with H3K4me2-marked nucleosome pairs were most enriched for NF-E2, FLI and RUNX sequence motifs, suggesting that this TF triad controls much of the late MK program. ChIP-seq revealed NF-E2 occupancy near previously implicated target genes, whose expression is compromised in Nfe2-null cells, and many other genes that become active late in MK differentiation. FLI and RUNX were also the motifs most enriched near NF-E2 binding sites and ChIP-seq implicated FLI1 and RUNX1 in activation of late MK, including NF-E2-dependent, genes. Histones showed limited activation in regions of single TF binding, while enhancers that bind NF-E2 and either RUNX1, FLI1 or both TFs gave the highest signals for TF occupancy and H3K4me2; these enhancers associated best with genes activated late in MK maturation. Thus, three essential TFs co- occupy late-acting cis-elements and show evidence for additive activity at genes responsible for platelet assembly and release. These findings provide a rich dataset of TF and chromatin dynamics in primary MK and explain why individual TF losses cause thrombopocytopenia.
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| Overall design |
ChIP-Seq of key transcription factors in matured megakaryocytes
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| Contributor(s) |
Zang C, Luyten A, Shivdasani RA, Liu XS |
| Citation(s) |
27457419 |
| Submission date |
Nov 07, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Chongzhi Zang |
| Organization name |
University of Virginia
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| Street address |
P. O. Box 800717
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| City |
Charlottesville |
| State/province |
VA |
| ZIP/Postal code |
22908 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA179147 |
| SRA |
SRP017109 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE42108_RAW.tar |
2.1 Gb |
(http)(custom) |
TAR (of BED, WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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