| First Author | Artinger EL | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 29 | Pages | 12000-5 |
| PubMed ID | 23744037 | Mgi Jnum | J:198726 |
| Mgi Id | MGI:5499049 | Doi | 10.1073/pnas.1301278110 |
| Citation | Artinger EL, et al. (2013) An MLL-dependent network sustains hematopoiesis. Proc Natl Acad Sci U S A 110(29):12000-5 |
| abstractText | The histone methyltransferase Mixed Lineage Leukemia (MLL) is essential to maintain hematopoietic stem cells and is a leukemia protooncogene. Although clustered homeobox 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-dependent 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, PR-domain containing 16 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. |
