Abstract
Many lineage-specific developmental regulator genes are transcriptionally primed in embryonic stem (ES) cells; RNA PolII is bound at their promoters but is prevented from productive elongation by the activity of polycomb repressive complexes (PRC) 1 and 2. This epigenetically poised state is thought to enable ES cells to rapidly execute multiple differentiation programs and is recognized by a simultaneous enrichment for trimethylation of lysine 4 and trimethylation of lysine 27 of histone H3 (bivalent chromatin) across promoter regions. Here we show that the chromatin profile of this important cohort of genes is progressively modified as ES cells differentiate toward blood-forming precursors. Surprisingly however, neural specifying genes, such as Nkx2-2, Nkx2-9, and Sox1, remain bivalent and primed even in committed hemangioblasts, as conditional deletion of PRC1 results in overt and inappropriate expression of neural genes in hemangioblasts. These data reinforce the importance of PRC1 for normal hematopoietic differentiation and reveal an unexpected epigenetic plasticity of mesoderm-committed hemangioblasts.
| Original language | English |
|---|---|
| Pages (from-to) | 83-87 |
| Number of pages | 5 |
| Journal | Blood |
| Volume | 117 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 6 2011 |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
Embryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression. / Mazzarella, Luca; Jørgensen, Helle F.; Soza-Ried, Jorge; Terry, Anna V.; Pearson, Stella; Lacaud, Georges; Kouskoff, Valerie; Merkenschlager, Matthias; Fisher, Amanda G.
In: Blood, Vol. 117, No. 1, 06.01.2011, p. 83-87.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Embryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression
AU - Mazzarella, Luca
AU - Jørgensen, Helle F.
AU - Soza-Ried, Jorge
AU - Terry, Anna V.
AU - Pearson, Stella
AU - Lacaud, Georges
AU - Kouskoff, Valerie
AU - Merkenschlager, Matthias
AU - Fisher, Amanda G.
PY - 2011/1/6
Y1 - 2011/1/6
N2 - Many lineage-specific developmental regulator genes are transcriptionally primed in embryonic stem (ES) cells; RNA PolII is bound at their promoters but is prevented from productive elongation by the activity of polycomb repressive complexes (PRC) 1 and 2. This epigenetically poised state is thought to enable ES cells to rapidly execute multiple differentiation programs and is recognized by a simultaneous enrichment for trimethylation of lysine 4 and trimethylation of lysine 27 of histone H3 (bivalent chromatin) across promoter regions. Here we show that the chromatin profile of this important cohort of genes is progressively modified as ES cells differentiate toward blood-forming precursors. Surprisingly however, neural specifying genes, such as Nkx2-2, Nkx2-9, and Sox1, remain bivalent and primed even in committed hemangioblasts, as conditional deletion of PRC1 results in overt and inappropriate expression of neural genes in hemangioblasts. These data reinforce the importance of PRC1 for normal hematopoietic differentiation and reveal an unexpected epigenetic plasticity of mesoderm-committed hemangioblasts.
AB - Many lineage-specific developmental regulator genes are transcriptionally primed in embryonic stem (ES) cells; RNA PolII is bound at their promoters but is prevented from productive elongation by the activity of polycomb repressive complexes (PRC) 1 and 2. This epigenetically poised state is thought to enable ES cells to rapidly execute multiple differentiation programs and is recognized by a simultaneous enrichment for trimethylation of lysine 4 and trimethylation of lysine 27 of histone H3 (bivalent chromatin) across promoter regions. Here we show that the chromatin profile of this important cohort of genes is progressively modified as ES cells differentiate toward blood-forming precursors. Surprisingly however, neural specifying genes, such as Nkx2-2, Nkx2-9, and Sox1, remain bivalent and primed even in committed hemangioblasts, as conditional deletion of PRC1 results in overt and inappropriate expression of neural genes in hemangioblasts. These data reinforce the importance of PRC1 for normal hematopoietic differentiation and reveal an unexpected epigenetic plasticity of mesoderm-committed hemangioblasts.
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U2 - 10.1182/blood-2010-03-273128
DO - 10.1182/blood-2010-03-273128
M3 - Article
C2 - 20876850
AN - SCOPUS:78650970000
VL - 117
SP - 83
EP - 87
JO - Blood
JF - Blood
SN - 0006-4971
IS - 1
ER -