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| Status |
Public on Dec 21, 2021 |
| Title |
BCL11A promotes myeloid leukemogenesis by abrogating the transcriptional activity of PU.1 [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| 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.
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| |
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| Overall design |
Examination of binding sites of 2 transcription factors and Histone H3K27ac in a single cell line
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| |
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| Contributor(s) |
Sunami Y, Nakamura T |
| Citation(s) |
34714913 |
| |
| Submission date |
Mar 30, 2020 |
| Last update date |
Mar 22, 2022 |
| Contact name |
Takuro Nakamura |
| E-mail(s) |
takuro-ind@umin.net
|
| 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 |
| |
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| Platforms (1) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE147798 |
BCL11A promotes myeloid leukemogenesis by abrogating the transcriptional activity of PU.1 |
|
| Relations |
| BioProject |
PRJNA616362 |
| SRA |
SRP254662 |
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