Chromatin modifications induced by PML-RARα repress critical targets in leukemogenesis as analyzed by ChIP-Chip
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The translocation t(15;17) generates the chimeric PML-RARα transcription factor that is the initiating event of acute promyelocytic leukemia. A global view of PML-RARα transcriptional functions was obtained by genome-wide binding and chromatin modification analyses combined with genome-wide expression data. Chromatin immunoprecipitation (ChIP)–chip experiments identified 372 direct genomic PML-RARα targets. A subset of these was confirmed in primary acute promyelocytic leukemia. Direct PML-RARα targets include regulators of global transcriptional programs as well as critical regulatory genes for basic cellular functions such as cell-cycle control and apoptosis. PML-RARα binding universally led to HDAC1 recruitment, loss of histone H3 acetylation, increased tri-methylation of histone H3 lysine 9, and unexpectedly increased trimethylation of histone H3 lysine 4. The binding of PML-RARα to target promoters and the resulting histone modifications resulted in mRNA repression of functionally relevant genes. Taken together, our results reveal that the transcription factor PML-RARα regulates key cancer-related genes and pathways by inducing a repressed chromatin formation on its direct genomic target genes.
Date Issued
2008-03-01
Date Acceptance
2007-11-05
Citation
Blood, 2008, 111 (5), pp.2887-2895
ISSN
0006-4971
Publisher
American Society of Hematology
Start Page
2887
End Page
2895
Journal / Book Title
Blood
Volume
111
Issue
5
Copyright Statement
"This research was originally published in Blood. Claudia Hoemme, Abdul Peerzada, Gerhard Behre, Yipeng Wang, Michael McClelland, Kay Nieselt, Matthias Zschunke, Christine Disselhoff, Shuchi Agrawal, Fabienne Isken, Nicola Tidow, Wolfgang E. Berdel, Hubert Serve, Carsten Müller-Tidow; Chromatin modifications induced by PML-RARα repress critical targets in leukemogenesis as analyzed by ChIP-Chip. Blood 2008; 111 (5): 2887–2895. doi: https://doi.org/10.1182/blood-2007-03-079921 © the American Society of Hematology."
Identifier
10.1182/blood-2007-03-
Publication Status
Published
Date Publish Online
2007-11-16