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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 13, 2011 |
| Title |
Harnessing of the Nucleosome Remodeling Deacetylase complex controls lymphocyte development and prevents leukemogenesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Cell fate decisions depend on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2u Nucleosome Remodeling and Deacetylase (NuRD) complex is controlled by the Ikaros family of lymphoid-lineage determining proteins. Ikaros, an integral component of the NuRD complex in lymphocytes, tethers this complex to active lymphoid differentiation genes, but keeps it in a functionally-poised state. Loss in Ikaros DNA binding activity causes a local increase in Mi-2u chromatin remodeling, histone deacetylation and suppression of lymphoid gene expression. The NuRD complex also redistributes to transcriptionally-poised non-Ikaros gene targets, involved in proliferation and metabolism, inducing their re-activation. Thus release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally-opposing epigenetic mechanisms and genetic networks.
We used microarrays to detail the global programme of gene expression of mouse DP thymocyte after Ikaros inactivation with dominant negative of Ik at different stage.
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| Overall design |
8 samples (mouse DP thymocytes from wt, and different stage after Ikaros inactivation) are analyzed Mouse Microarray Expression platforms, Affymetrix Mouse 430 2.0. Examination of different histone modifications and binding sites for Ikaros, Mi2beta in wild type DP thymocytes, and Ikaros knockout thymocytes.
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| Contributor(s) |
Zhang J, Jackson AF, Naito T, Seavitt J, Heller EJ, Liu F, Dose M, Kashiwagi M, Yoshida T, Gounari F, Petrie H, Georgopoulos K |
| Citation(s) |
22080921 |
| Submission date |
Sep 22, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Jiangwen Zhang |
| E-mail(s) |
jzhang@cgr.harvard.edu
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| Organization name |
Harvard University
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| Department |
FAS Center for Systems Biology
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| Street address |
7 Divinity Ave
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02138 |
| Country |
USA |
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| Platforms (2) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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| Samples (33)
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| GSM800503 |
Ikaros KO thymocyte stage 1, biological rep1 |
| GSM800504 |
Ikaros KO thymocyte stage 1, biological rep2 |
| GSM800505 |
Ikaros KO thymocyte stage 1, biological rep3 |
| GSM800506 |
Ikaros dominant negative thymocyte stage 2 (16 d), biological rep1 |
| GSM800507 |
Ikaros dominant negative thymocyte stage 2 (16 d), biological rep2 |
| GSM802973 |
Ikaros dominant negative thymocyte stage 2 (27 d), biological rep1 |
| GSM802974 |
Ikaros dominant negative thymocyte stage 2 (27 d), biological rep2 |
| GSM802975 |
Ikaros dominant negative thymocyte stage 3, biological rep1 |
| GSM803106 |
Aio Ikaros knockout chromatin |
| GSM803107 |
input DNA Ikaros knockout chromatin |
| GSM803108 |
Mi2beta Ikaros knockout chromatin |
| GSM803109 |
input wildtype 1and2 |
| GSM803110 |
Ikaros wildtype 1and2 |
| GSM803111 |
Mi2beta wildtype 1and2 |
| GSM803112 |
H3K4me3 wildtype |
| GSM803113 |
H3K27me3 wildtype |
| GSM803114 |
H3K9ac2 wildtype |
| GSM803115 |
H3K36me3 wildtype |
| GSM803116 |
PolII wildtype |
| GSM803117 |
H3K4me3 Ikaros knockout chromatin stageI |
| GSM803118 |
H3K27me3 Ikaros knockout chromatin stageI |
| GSM803119 |
H3K9ac2 Ikaros knockout chromatin stageI |
| GSM803120 |
H3K36me3 Ikaros knockout chromatin stageI |
| GSM803121 |
input DNA Ikaros knockout chromatin preleukemic stage1 |
| GSM803122 |
H3K4me3 Ikaros knockout chromatin preleukemic stage2 |
| GSM803123 |
H3K27me3 Ikaros knockout chromatin preleukemic stage2 |
| GSM803124 |
H3K9ac2 Ikaros knockout chromatin preleukemic stage2 |
| GSM803125 |
H3K36me3 Ikaros knockout chromatin preleukemic stage2 |
| GSM803126 |
PolII Ikaros knockout chromatin preleukemic stage2 |
| GSM803127 |
input DNA Ikaros knockout chromatin preleukemic stage2 |
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| Relations |
| SRA |
SRP008553 |
| BioProject |
PRJNA147297 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE32311_RAW.tar |
1.5 Gb |
(http)(custom) |
TAR (of BED, CEL, WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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