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The Polycomb Group Protein L3MBTL1 Represses a SMAD5-Mediated Hematopoietic Transcriptional Program in Human Pluripotent Stem Cells
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 i...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400644/ https://www.ncbi.nlm.nih.gov/pubmed/25754204 http://dx.doi.org/10.1016/j.stemcr.2015.02.003 |
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author | Perna, Fabiana Vu, Ly P. Themeli, Maria Kriks, Sonja Hoya-Arias, Ruben Khanin, Raya Hricik, Todd Mansilla-Soto, Jorge Papapetrou, Eirini P. Levine, Ross L. Studer, Lorenz Sadelain, Michel Nimer, Stephen D. |
author_facet | Perna, Fabiana Vu, Ly P. Themeli, Maria Kriks, Sonja Hoya-Arias, Ruben Khanin, Raya Hricik, Todd Mansilla-Soto, Jorge Papapetrou, Eirini P. Levine, Ross L. Studer, Lorenz Sadelain, Michel Nimer, Stephen D. |
author_sort | Perna, Fabiana |
collection | PubMed |
description | 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 populations, 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. |
format | Online Article Text |
id | pubmed-4400644 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-44006442015-04-22 The Polycomb Group Protein L3MBTL1 Represses a SMAD5-Mediated Hematopoietic Transcriptional Program in Human Pluripotent Stem Cells Perna, Fabiana Vu, Ly P. Themeli, Maria Kriks, Sonja Hoya-Arias, Ruben Khanin, Raya Hricik, Todd Mansilla-Soto, Jorge Papapetrou, Eirini P. Levine, Ross L. Studer, Lorenz Sadelain, Michel Nimer, Stephen D. Stem Cell Reports Article 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 populations, 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. Elsevier 2015-03-05 /pmc/articles/PMC4400644/ /pubmed/25754204 http://dx.doi.org/10.1016/j.stemcr.2015.02.003 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
spellingShingle | Article Perna, Fabiana Vu, Ly P. Themeli, Maria Kriks, Sonja Hoya-Arias, Ruben Khanin, Raya Hricik, Todd Mansilla-Soto, Jorge Papapetrou, Eirini P. Levine, Ross L. Studer, Lorenz Sadelain, Michel Nimer, Stephen D. The Polycomb Group Protein L3MBTL1 Represses a SMAD5-Mediated Hematopoietic Transcriptional Program in Human Pluripotent Stem Cells |
title | The Polycomb Group Protein L3MBTL1 Represses a SMAD5-Mediated Hematopoietic Transcriptional Program in Human Pluripotent Stem Cells |
title_full | The Polycomb Group Protein L3MBTL1 Represses a SMAD5-Mediated Hematopoietic Transcriptional Program in Human Pluripotent Stem Cells |
title_fullStr | The Polycomb Group Protein L3MBTL1 Represses a SMAD5-Mediated Hematopoietic Transcriptional Program in Human Pluripotent Stem Cells |
title_full_unstemmed | The Polycomb Group Protein L3MBTL1 Represses a SMAD5-Mediated Hematopoietic Transcriptional Program in Human Pluripotent Stem Cells |
title_short | The Polycomb Group Protein L3MBTL1 Represses a SMAD5-Mediated Hematopoietic Transcriptional Program in Human Pluripotent Stem Cells |
title_sort | polycomb group protein l3mbtl1 represses a smad5-mediated hematopoietic transcriptional program in human pluripotent stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400644/ https://www.ncbi.nlm.nih.gov/pubmed/25754204 http://dx.doi.org/10.1016/j.stemcr.2015.02.003 |
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