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| Status |
Public on Nov 11, 2015 |
| Title |
MLL5 Orchestrates a Cancer Self-Renewal State by Repressing the Histone Variant H3.3 and Globally Reorganizing Chromatin [expression] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Mutations in the histone 3 variant H3.3 have been identified in one-third of pediatric glioblastomas (GBMs), but not in adult tumors. Here we show that H3.3 is a dynamic determinant of functional properties in adult GBM. H3.3 is repressed by mixed lineage leukemia 5 (MLL5) in self-renewing GBM cells. MLL5 is a global epigenetic repressor that orchestrates reorganization of chromatin structure by punctuating chromosomes with foci of compacted chromatin, favoring tumorigenic and self-renewing properties. Conversely, H3.3 antagonizes self-renewal and promotes differentiation. We exploited these epigenetic states to rationally identify two small molecules that effectively curb cancer stem cell properties in a preclinical model. Our work uncovers a role for MLL5 and H3.3 in maintaining self-renewal hierarchies in adult GBM.
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| Overall design |
MLL5 was over-expressed in the GBM primary culture G514NS. EGFP was expressed from the same vector backbone as a control. N = 3 biological replicates for each of EGFP- and MLL5-overexpressing cells.
Please note that complete data output (with 74,342 data rows) from Partek analysis contains several identifiers which are not represented in the GPL17586, and therefore is linked as Series supplementary file.
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| |
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| Contributor(s) |
Gallo M, Dirks PB |
| Citation(s) |
26626085 |
| Submission date |
Nov 14, 2014 |
| Last update date |
Oct 29, 2018 |
| Contact name |
Marco Gallo |
| E-mail(s) |
marco.gallo@ucalgary.ca
|
| Organization name |
University of Calgary
|
| Department |
Cumming School of Medicine
|
| Street address |
3330 Hospital Dr NW
|
| City |
Calgary |
| State/province |
AB |
| ZIP/Postal code |
T2N 4N1 |
| Country |
Canada |
| |
|
| Platforms (1) |
| GPL17586 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version] |
|
| Samples (6)
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| GSM1545195 |
EGFP-expressing cells, biological rep 1 |
| GSM1545196 |
EGFP-expressing cells, biological rep 2 |
| GSM1545197 |
EGFP-expressing cells, biological rep 3 |
| GSM1545198 |
MLL5-overexpressing cells, biological rep 1 |
| GSM1545199 |
MLL5-overexpressing cells, biological rep 2 |
| GSM1545200 |
MLL5-overexpressing cells, biological rep 3 |
|
| Relations |
| BioProject |
PRJNA267217 |
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