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Series GSE147797 Query DataSets for GSE147797
Status Public on Dec 21, 2021
Title BCL11A promotes myeloid leukemogenesis by abrogating the transcriptional activity of PU.1 [array]
Organism Mus musculus
Experiment type Expression profiling by array
Summary The transcriptional repressor Bcl11a is involved in hematological malignancies, B-cell development and fetal to adult hemoglobin switching, however, the molecular mechanism how Bcl11a promotes development of myeloid leukemia remains largely unknown. We found that Bcl11a cooperates with the pseudokinase Trib1 in AML development. Bcl11a promotes proliferation of Trib1-expressing AML cells both in vitro and in vivo. ChIP-seq analysis showed that Bcl11a is significantly associated on DNA-binding with PU.1 that promotes myeloid differentiation, and Bcl11a represses a number of PU.1 target genes such as Clec5a, Fcgr3 and Csf1r. The repression of PU.1 target genes by Bcl11a is achieved by both sequence-specific DNA binding activity and recruitment of corepressors by Bcl11a, and suppression of corepressor components HDAC1 and LSD1 cancelled the repressive activity. Association of high level of expression of BCL11A and worse prognosis is observed in human AML patients, and blocking of BCL11A expression upregulates PU.1 target expression, inhibits engraftment to bone marrow, and enhances myeloid differentiation of HL-60 cells, suggesting that BCL11A is involved in human myeloid malignancies via the PU.1 transcriptional activity.
We used microarrays to detail the global program of gene expression in mouse AML
Overall design Murine AML cell lines expressing Trib1 with or without Bcl11a were examined.
Contributor(s) Sunami Y, Nakamura T
Citation(s) 34714913
Submission date Mar 30, 2020
Last update date Mar 22, 2022
Contact name Takuro Nakamura
Phone 81-3-3570-0462
Organization name Japanese Foundation for Cancer Research
Department The Cancer Institute
Lab Carcinogenesis
Street address 3-8-31 Ariake, Koto-ku
City Tokyo
ZIP/Postal code 135-8550
Country Japan
Platforms (1)
GPL11180 [HT_MG-430_PM] Affymetrix HT MG-430 PM Array Plate
Samples (12)
GSM4446319 Trib1 1
GSM4446320 Trib1 2
GSM4446321 Trib1 3
This SubSeries is part of SuperSeries:
GSE147798 BCL11A promotes myeloid leukemogenesis by abrogating the transcriptional activity of PU.1
BioProject PRJNA616393

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE147797_RAW.tar 25.3 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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