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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ernst, Patricia Zaffuto, Kristin M. Li, Bin E. Moore, Adrian W. Chen, Yufei Chung, Elaine K. Y. Artinger, Erika L. Mishra, Bibhu P. Cheng, Chao |
| Description | Author Affiliation: Artinger EL ( Department of Genetics , Institute for Quantitative Biomedical Sciences, and Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.); |
| Abstract | 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 29 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Epigenesis, Genetic Physiology Gene Regulatory Networks Hematopoiesis Hematopoietic Stem Cells Myeloid-Lymphoid Leukemia Protein Chromatin Immunoprecipitation Histone-Lysine N-Methyltransferase Models, Biological Proto-Oncogene Proteins Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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