Integrated genome-wide chromatin occupancy and expression analyses identify key myeloid pro-differentiation transcription factors repressed by Myb

Zhao, Liang, Glazov, Evgeny, Diwakar Ram Pattabiraman, Al-Owaidi, Faisal, Ping Zhang, Brown, Matthew A., Paul Leo and Gonda, Thomas J. (2011) Integrated genome-wide chromatin occupancy and expression analyses identify key myeloid pro-differentiation transcription factors repressed by Myb. Nucleic Acids Research, 39 11: 4664-4679. doi:10.1093/nar/gkr024

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Author Zhao, Liang
Glazov, Evgeny
Diwakar Ram Pattabiraman
Al-Owaidi, Faisal
Ping Zhang
Brown, Matthew A.
Paul Leo
Gonda, Thomas J.
Title Integrated genome-wide chromatin occupancy and expression analyses identify key myeloid pro-differentiation transcription factors repressed by Myb
Journal name Nucleic Acids Research   Check publisher's open access policy
ISSN 0305-1048
1362-4962
Publication date 2011-06-01
Sub-type Article (original research)
DOI 10.1093/nar/gkr024
Open Access Status DOI
Volume 39
Issue 11
Start page 4664
End page 4679
Total pages 16
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
To gain insight into the mechanisms by which the Myb transcription factor controls normal hematopoiesis and particularly, how it contributes to leukemogenesis, we mapped the genome-wide occupancy of Myb by chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) in ERMYB myeloid progenitor cells. By integrating the genome occupancy data with whole genome expression profiling data, we identified a Myb-regulated transcriptional program. Gene signatures for leukemia stem cells, normal hematopoietic stem/progenitor cells and myeloid development were overrepresented in 2368 Myb regulated genes. Of these, Myb bound directly near or within 793 genes. Myb directly activates some genes known critical in maintaining hematopoietic stem cells, such as Gfi1 and Cited2. Importantly, we also show that, despite being usually considered as a transactivator, Myb also functions to repress approximately half of its direct targets, including several key regulators of myeloid differentiation, such as Sfpi1 (also known as Pu.1), Runx1, Junb and Cebpb. Furthermore, our results demonstrate that interaction with p300, an established coactivator for Myb, is unexpectedly required for Mybmediated transcriptional repression. We propose that the repression of the above mentioned key pro-differentiation factors may contribute essentially to Myb’s ability to suppress differentiation and promote self-renewal, thus maintaining progenitor cells in an undifferentiated state and promoting leukemic transformation.
Keyword MYB transcription factor
Leukemia
Cancer
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 11 February 2011.

 
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Created: Sat, 12 Mar 2011, 00:59:14 EST by Susan Allen on behalf of UQ Diamantina Institute