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Series GSE43725 Query DataSets for GSE43725
Status Public on Feb 19, 2013
Title The histone H2B ubiquitin ligase RNF20 is required for MLL-rearranged leukemia
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary MLL-fusions are potent oncogenes that initiate aggressive forms of acute leukemia. As aberrant transcriptional regulators, MLL-fusion proteins alter gene expression in hematopoietic cells through interactions with the histone H3 lysine 79 (H3K79) methyltransferase DOT1L. Notably, interference with MLL-fusion cofactors like DOT1L is an emerging therapeutic strategy in this disease. Here we identify the histone H2B E3 ubiquitin ligase RNF20 as an additional requirement for MLL-fusion-mediated leukemogenesis. Suppressing the expression of Rnf20 in diverse models of MLL-rearranged leukemia leads to inhibition of cell proliferation; under tissue culture conditions as well as in vivo. Rnf20 knockdown leads to reduced expression of MLL-fusion target genes, including Hoxa9 and Meis1; effects that resemble Dot1l-inhibition. Using ChIP-seq, we found that H2B ubiquitination (H2Bub) is enriched in the body of MLL-fusion target genes, correlating with sites of H3K79 methylation and transcription elongation. Furthermore, we found that Rnf20 is required to maintain local levels of H3K79 di-methylation by Dot1l at Hoxa9 and Meis1. These findings support a model whereby co-transcriptional recruitment of Rnf20 at MLL-fusion target genes leads to amplification of Dot1l-mediated H3K79 methylation, thereby rendering leukemia cells dependent on Rnf20 to maintain their oncogenic transcriptional program.
Overall design Examination of gene expression profiles upon RNF20 RNAi in MLL-AF9 acute myeloid leukemia cells
Contributor(s) Kawaoka S, Vakoc C
Citation(s) 23412334
Submission date Jan 24, 2013
Last update date May 15, 2019
Contact name Shinpei Kawaoka
Phone 631-327-4269
Organization name Cold Spring Harbor Laboratory
Street address 1 Bungtown road
City Cold Spring Harbor
ZIP/Postal code 11724
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (3)
GSM1069722 RN2/shRen.713
GSM1069723 RN2/shRnf20.3277
GSM1069724 RN2/shRnf20.3595
BioProject PRJNA187484
SRA SRP018248

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Supplementary file Size Download File type/resource
GSE43725_RAW.tar 740.0 Kb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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