Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

The Polycomb protein Pcgf2/Mel18 regulates mesoderm cell fate-specification of embryonic stem cells through multiple mechanisms

ABSTRACT: Polycomb complexes are essential regulators of stem cell identity, yet very little is known about their molecular mechanisms during cell differentiation. Pcgf proteins (Pcgf1/2/3/4/5/6) are core subunits of the Polycomb repressive complex 1 (PRC1). It has been recently proposed that specific Pcgf proteins are associated to particular PRC1 complexes, yet the molecular and biological functions of different Pcgf proteins remains largely elusive. Using specific differentiation protocols, we have elucidated a role for Pcgf2/Mel18 in specifically regulating mesoderm differentiation. Mechanistically, during early cardiac mesoderm differentiation, Pcgf2/Mel18 functions as a classical Polycomb protein by repressing pluripotency, lineage specification, late cardiac differentiation and negative regulators of the BMP pathway, yet Pcgf2/Mel18 also positively regulates the expression of key mesoderm transcription factors, revealing a novel function of Pcgf2/Mel18 in gene activation during cardiac differentiation. Mel18 depletion results in an unbalance of pathways that positively and negatively regulate cardiac differentiation. We propose that Mel18 is a novel epigenetic factor that controls mesoderm differentiation by opposing molecular mechanisms. List of ChIPseq samples: Mel18 in ESCs and MES, Ring1b, RYBP and Cbx2 in MES, IgG in MESs. List of RNAseq experiments: Mel18 KD, Ring1b KO and CTR in ESCs, Mel18 KD and CTR in MES, Mel18 KD and CTR in CMs.

ORGANISM(S): Mus musculus

SUBMITTER: Enrique Blanco

PROVIDER: E-GEOD-67868 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Polycomb Regulates Mesoderm Cell Fate-Specification in Embryonic Stem Cells through Activation and Repression Mechanisms.

Morey Lluis L Santanach Alexandra A Blanco Enrique E Aloia Luigi L Nora Elphège P EP Bruneau Benoit G BG Di Croce Luciano L

Cell stem cell 20150901 3

Polycomb complexes (PRC1 and PRC2) are essential regulators of epigenetic gene silencing in embryonic and adult stem cells. Emerging evidence suggests that the core subunit composition regulates distinct biological processes, yet little is known about the mechanistic underpinnings of how differently composed Polycomb complexes instruct and maintain cell fate. Here we find that Mel18, also known as Pcgf2 and one of six Pcgf paralogs, uniquely regulates PRC1 to specify mesoderm cell fate in embryo ...[more]

PMID: 26340528

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Dataset Information

The Polycomb protein Pcgf2/Mel18 regulates mesoderm cell fate-specification of embryonic stem cells through multiple mechanisms

Publications

Polycomb Regulates Mesoderm Cell Fate-Specification in Embryonic Stem Cells through Activation and Repression Mechanisms.

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