Dataset: MLL regulated genes in LSK/CD48- hematopoietic stem cells

The histone methyltransferase mixed lineage leukemia (MLL) is essential to maintain hematopoietic stem cells and is a leukemia protooncogene. Although Hox genes are well-characterized targets of MLL and MLL fusion oncoproteins, the range of Mll-regulated genes in normal hematopoietic cells remains unknown. Here we identify and characterize part of the Mll-transcriptional network in hematopoietic stem cells with an integrated approach by using conditional loss-of-function models, genomewide expression analyses, chromatin immunoprecipitation, and functional rescue assays. The Mll-dependent transcriptional network extends well beyond the previously appreciated Hox targets, is comprised of many characterized regulators of self-renewal, and contains target genes that are both dependent and independent of the MLL cofactor, Menin. Interestingly, Prdm16 emerged as a target gene that is uniquely effective at partially rescuing Mll-deficient hematopoietic stem and progenitor cells. This work highlights the tissue-specific nature of regulatory networks under the control of MLL/Trithorax family members and provides insight into the distinctions between the participation of MLL in normal hematopoiesis and in leukemia. We used microarrays to determine the gene expression profiles of HSCs upon conditional deletion of Mll. LSK/CD48- HSCs were sorted from 5 pI:pC injected MllF/F control mice or 5 pI:pC injected Mx1-cre;MllF/F mice 6 days after the initial injection. Total RNA was purified from 1,500 to 10,000 sorted cells, amplified, labeled, fragmented and hybridized to GeneChip Mouse Genome 430 2.0 arrays from Affymetrix.

Species:

mouse

Samples:

10

Source:

E-GEOD-47205

Updated:

Dec.12, 2014

Registered:

Nov.12, 2014