Please use this identifier to cite or link to this item:
|Title:||Characterisation of genome-wide PLZF/RARA target genes|
|Citation:||Spicuglia, S., Vincent-Fabert, C., Benoukraf, T., Tibéri, G., Saurin, A.J., Zacarias-Cabeza, J., Grimwade, D., Mills, K., Calmels, B., Bertucci, F., Sieweke, M., Ferrier, P., Duprez, E. (2011-09-20). Characterisation of genome-wide PLZF/RARA target genes. PLoS ONE 6 (9) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0024176|
|Abstract:||The PLZF/RARA fusion protein generated by the t(11;17)(q23;q21) translocation in acute promyelocytic leukaemia (APL) is believed to act as an oncogenic transcriptional regulator recruiting epigenetic factors to genes important for its transforming potential. However, molecular mechanisms associated with PLZF/RARA-dependent leukaemogenesis still remain unclear. We searched for specific PLZF/RARA target genes by ChIP-on-chip in the haematopoietic cell line U937 conditionally expressing PLZF/RARA. By comparing bound regions found in U937 cells expressing endogenous PLZF with PLZF/RARA-induced U937 cells, we isolated specific PLZF/RARA target gene promoters. We next analysed gene expression profiles of our identified target genes in PLZF/RARA APL patients and analysed DNA sequences and epigenetic modification at PLZF/RARA binding sites. We identify 413 specific PLZF/RARA target genes including a number encoding transcription factors involved in the regulation of haematopoiesis. Among these genes, 22 were significantly down regulated in primary PLZF/RARA APL cells. In addition, repressed PLZF/RARA target genes were associated with increased levels of H3K27me3 and decreased levels of H3K9K14ac. Finally, sequence analysis of PLZF/RARA bound sequences reveals the presence of both consensus and degenerated RAREs as well as enrichment for tissue-specific transcription factor motifs, highlighting the complexity of targeting fusion protein to chromatin. Our study suggests that PLZF/RARA directly targets genes important for haematopoietic development and supports the notion that PLZF/RARA acts mainly as an epigenetic regulator of its direct target genes. © 2011 Spicuglia et al.|
|Source Title:||PLoS ONE|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Mar 26, 2019
WEB OF SCIENCETM
checked on Mar 26, 2019
checked on Mar 22, 2019
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.