Embryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression

Luca Mazzarella, Helle F. Jørgensen, Jorge Soza-Ried, Anna V. Terry, Stella Pearson, Georges Lacaud, Valerie Kouskoff, Matthias Merkenschlager, Amanda G. Fisher

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)83-87
Number of pages5
JournalBlood
Volume117
Issue number1
DOIs
Publication statusPublished - Jan 6 2011

Fingerprint

Hemangioblasts
Embryonic Stem Cells
Stem cells
Gene expression
Plastics
Genes
Gene Expression
Lysine
Chromatin
Polycomb Repressive Complex 1
Polycomb Repressive Complex 2
Developmental Genes
Mesoderm
Regulator Genes
Genetic Promoter Regions
Epigenomics
Histones
RNA
Plasticity
Elongation

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 journalArticle

Mazzarella, L, Jørgensen, HF, Soza-Ried, J, Terry, AV, Pearson, S, Lacaud, G, Kouskoff, V, Merkenschlager, M & Fisher, AG 2011, 'Embryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression', Blood, vol. 117, no. 1, pp. 83-87. https://doi.org/10.1182/blood-2010-03-273128
Mazzarella, Luca ; Jørgensen, Helle F. ; Soza-Ried, Jorge ; Terry, Anna V. ; Pearson, Stella ; Lacaud, Georges ; Kouskoff, Valerie ; Merkenschlager, Matthias ; Fisher, Amanda G. / Embryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression. In: Blood. 2011 ; Vol. 117, No. 1. pp. 83-87.
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