The polycomb group protein L3MBTL1 represses a SMAD5-mediated hematopoietic transcriptional program in human pluripotent stem cells Journal Article
| Authors: | Perna, F.; Vu, L. P.; Themeli, M.; Kriks, S.; Hoya-Arias, R. ; Khanin, R.; Hricik, T.; Mansilla-Soto, J.; Papapetrou, E. P.; Levine, R. L.; Studer, L.; Sadelain, M.; Nimer, S. D. |
| Article Title: | The polycomb group protein L3MBTL1 represses a SMAD5-mediated hematopoietic transcriptional program in human pluripotent stem cells |
| Abstract: | Epigenetic regulation of key transcriptional programs is a critical mechanism that controls hematopoietic development, and, thus, aberrant expression patterns or mutations in epigenetic regulators occur frequently in hematologic malignancies. We demonstrate that the Polycomb protein L3MBTL1, which is monoallelically deleted in 20q- myeloid malignancies, represses the ability of stem cells to drive hematopoietic-specific transcriptional programs by regulating the expression of SMAD5 and impairing its recruitment to target regulatory regions. Indeed, knockdown of L3MBTL1 promotes the development of hematopoiesis and impairs neural cell fate in human pluripotent stem cells. We also found a role for L3MBTL1 in regulating SMAD5 target gene expression in mature hematopoietic cell pop-ulations, thereby affecting erythroid differentiation. Taken together, we have identified epigenetic priming of hematopoietic-specific transcriptional networks, which may assist in the development of therapeutic approaches for patients with anemia. |
| Keywords: | controlled study; unclassified drug; gene mutation; human cell; anemia; smad5 protein; cell fate; neural stem cell; cell differentiation; gene expression regulation; hematologic malignancy; transcription regulation; epigenetics; nucleotide sequence; erythroid cell; hematopoiesis; pluripotent stem cell; hematopoietic stem cell; chromosome deletion; polycomb group protein; chromosome 20q; protein l3mbtl1; human; priority journal; article |
| Journal Title: | Stem Cell Reports |
| Volume: | 4 |
| Issue: | 4 |
| ISSN: | 2213-6711 |
| Publisher: | Cell Press |
| Date Published: | 2015-04-14 |
| Start Page: | 658 |
| End Page: | 669 |
| Language: | English |
| DOI: | 10.1016/j.stemcr.2015.02.003 |
| PROVIDER: | scopus |
| PMCID: | PMC4400644 |
| PUBMED: | 25754204 |
| DOI/URL: | |
| Notes: | Export Date: 3 August 2015 -- Source: Scopus |
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