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| Status |
Public on Sep 08, 2013 |
| Title |
Selective Functions of Individual Zinc Fingers Within the DNA-Binding Domain of Ikaros (ChIP-seq: Thymocytes) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The C2H2 zinc finger is the most prevalent DNA-binding motif in the mammalian proteome, with DNA-binding domains usually containing more tandem fingers than are needed for stable sequence-specific DNA recognition. To examine the reason for the frequent presence of multiple zinc fingers, we generated mice lacking finger 1 or finger 4 of the 4-finger DNA-binding domain of Ikaros, a critical regulator of lymphopoiesis and leukemogenesis. Each mutant strain exhibited a specific subset of the phenotypes observed with Ikaros null mice. Of particular relevance, fingers 1 and 4 contributed to distinct stages of B- and T-cell development and finger 4 was selectively required for tumor suppression in thymocytes and in a new model of BCR-ABL+ acute lymphoblastic leukemia. These results, combined with transcriptome profiling (this GEO submission: RNA-Seg of whole thymus from wt and the two ZnF mutants), reveal that different subsets of fingers within multi-finger transcription factors can regulate distinct target genes and biological functions, and they demonstrate that selective mutagenesis can facilitate efforts to elucidate the functions and mechanisms of action of this prevalent class of factors.
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| |
|
| Overall design |
Ikaros ChIP-Seq from Whole Thymus comparing wt, Ikaros-ZnF1-/- mutant and Ikaros-ZnF4-/- mutant
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| |
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| Contributor(s) |
Schjerven H, Smale ST |
| Citation(s) |
24013668 |
| |
| Submission date |
Nov 14, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Hilde Schjerven |
| Organization name |
UCSF
|
| Department |
Laboratory Medicine
|
| Street address |
513 Parnassus Ave
|
| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94143 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (6)
|
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| This SubSeries is part of SuperSeries: |
| GSE33693 |
Selective Functions of Individual Zinc Fingers Within the DNA-Binding Domain of Ikaros |
|
| Relations |
| SRA |
SRP009418 |
| BioProject |
PRJNA154205 |
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