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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 658-669 |
| Number of pages | 12 |
| Journal | Stem Cell Reports |
| Volume | 4 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2015 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Developmental Biology
- Genetics
Cite this
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.
In: Stem Cell Reports, Vol. 4, No. 4, 2015, p. 658-669.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The polycomb group protein L3MBTL1 repreßes a SMAD5-mediated hematopoietic transcriptional program in human pluripotent stem cells
AU - Perna, Fabiana
AU - Vu, Ly P.
AU - Themeli, Maria
AU - Kriks, Sonja
AU - Hoya-Arias, Ruben
AU - Khanin, Raya
AU - Hricik, Todd
AU - Mansilla-Soto, Jorge
AU - Papapetrou, Eirini P.
AU - Levine, Roß L.
AU - Studer, Lorenz
AU - Sadelain, Michel
AU - Nimer, Stephen D
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84933673346&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84933673346&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2015.02.003
DO - 10.1016/j.stemcr.2015.02.003
M3 - Article
C2 - 25754204
AN - SCOPUS:84933673346
VL - 4
SP - 658
EP - 669
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 4
ER -