 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Apr 28, 2011 |
| Title |
MLL Fusion Proteins Preferentially Regulate a Small Set of Wild Type MLL Target Genes in the Leukemic Genome |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by array
Genome binding/occupancy profiling by genome tiling array
|
| Summary |
MLL encodes a histone methyltransferase that is critical in maintaining gene expression during embryonic development and hematopoiesis. 11q23 translocations encode chimeric MLL fusions that act as potent drivers of acute leukemia. However, it remains unclear what portion of the leukemic genome is under the direct control of the MLL fusion protein. By comparing patient-derived leukemic cell lines, we find that MLL fusion-bound genes are a small subset of that recognized by wild-type MLL. In an inducible MLL-ENL cellular model, binding of the MLL fusion protein and changes in H3K79 methylation are limited to a specific portion of the genome, whereas wild-type MLL distributes to a much larger set of gene loci. Surprisingly, among 223 MLL fusion-bound genes, only 12 demonstrate a significant increase in mRNA expression upon induction of the fusion protein. In addition to Hoxa9 and Meis1, this includes Eya1 and Six1 which comprise a heterodimeric transcription factor important in several developmental pathways. We show that Eya1 has the capacity to immortalize hematopoietic progenitor cells in vitro and collaborates with Six1 in hematopoietic transformation assays. Altogether, our data suggest that MLL fusions contribute to the development of acute leukemia through direct activation of a small set of target genes.
|
| |
|
| Overall design |
We explored an inducible MLL-ENL cellular model, which was obtained from Dr. Robert Slany (University Erlangen, Germany). We wished to examine the differential expressed genes that are bound by MLL wild type (No 4-OHT) and fusion (4-OHT) proteins, combinding the ChIP-chip data to explore the potential MLL fusion-regulated genes.
|
| |
|
| Contributor(s) |
Wang Q, Wu G, Mi S, He F, Wu J, Dong J, Luo R, Mattison R, Kaberlein J, Wang Q, Prabhakar S, Ji H, Thirman MJ |
| Citation(s) |
21518926 |
| Submission date |
Oct 19, 2010 |
| Last update date |
Mar 06, 2018 |
| Contact name |
Jun Wu |
| E-mail(s) |
wuj@big.ac.cn
|
| Organization name |
Beijing Institue of Genomics, Chinese Academy of Science
|
| Street address |
No.7 Beitucheng West Road
|
| City |
Beijing |
| ZIP/Postal code |
100029 |
| Country |
China |
| |
|
| Platforms (3) |
| GPL6096 |
[MoEx-1_0-st] Affymetrix Mouse Exon 1.0 ST Array [transcript (gene) version] |
| GPL11070 |
NimbleGen custom Mouse 17K TSS array |
| GPL11071 |
NimbleGen custom Human HG18 144-gene region Array |
|
| Samples (32)
|
|
| Relations |
| BioProject |
PRJNA132281 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE24794_RAW.tar |
486.3 Mb |
(http)(custom) |
TAR (of CEL, PAIR) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...