Polycomb Group Protein Pcgf6 Acts as a Master Regulator to Maintain Embryonic Stem Cell Identity

Chao-Shun Yang; Kung-Yen Chang; Jason Dang; Tariq M Rana

doi:10.1038/srep26899

Polycomb Group Protein Pcgf6 Acts as a Master Regulator to Maintain Embryonic Stem Cell Identity

Sci Rep. 2016 Jun 1:6:26899. doi: 10.1038/srep26899.

Authors

Chao-Shun Yang¹, Kung-Yen Chang¹, Jason Dang², Tariq M Rana^{1

3}

Affiliations

¹ Department of Pediatrics, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, California, 92093, USA.
² Department of Bioengineering, University of California San Diego, La Jolla, California, 92093, USA.
³ Institute for Genomic Medicine and Moores Cancer Center, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, California, 92093, USA.

Abstract

The polycomb repressive complex 1 (PRC1) is a multi-subunit complex that plays critical roles in the epigenetic modulation of gene expression. Here, we show that the PRC1 component polycomb group ring finger 6 (Pcgf6) is required to maintain embryonic stem cell (ESC) identity. In contrast to canonical PRC1, Pcgf6 acts as a positive regulator of transcription and binds predominantly to promoters bearing active chromatin marks. Pcgf6 is expressed at high levels in ESCs, and knockdown reduces the expression of the core ESC regulators Oct4, Sox2, and Nanog. Conversely, Pcgf6 overexpression prevents downregulation of these factors and impairs differentiation. In addition, Pcgf6 enhanced reprogramming in both mouse and human somatic cells. The genomic binding profile of Pcgf6 is highly similar to that of trithorax group proteins, but not of PRC1 or PRC2 complexes, suggesting that Pcgf6 functions atypically in ESCs. Our data reveal novel roles for Pcgf6 in directly regulating Oct4, Nanog, Sox2, and Lin28 expression to maintain ESC identity.

MeSH terms

Animals
Cell Differentiation
Cellular Reprogramming*
Chromatin / chemistry
Chromatin / metabolism*
Embryo, Mammalian
Fibroblasts / cytology
Fibroblasts / metabolism
Gene Expression Regulation
Genes, Reporter
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Human Embryonic Stem Cells / cytology
Human Embryonic Stem Cells / metabolism*
Humans
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / metabolism*
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors / genetics
Kruppel-Like Transcription Factors / metabolism
Mice
Mice, Nude
Microarray Analysis
Mouse Embryonic Stem Cells / cytology
Mouse Embryonic Stem Cells / metabolism*
Octamer Transcription Factor-3 / genetics
Octamer Transcription Factor-3 / metabolism
Polycomb Repressive Complex 1 / genetics*
Polycomb Repressive Complex 1 / metabolism
Proto-Oncogene Proteins c-myc / genetics
Proto-Oncogene Proteins c-myc / metabolism
SOXB1 Transcription Factors / genetics
SOXB1 Transcription Factors / metabolism
Signal Transduction
Teratoma / genetics
Teratoma / metabolism
Teratoma / pathology

Substances

Chromatin
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors
Myc protein, mouse
Octamer Transcription Factor-3
Pcgf6 protein, mouse
Pou5f1 protein, mouse
Proto-Oncogene Proteins c-myc
SOXB1 Transcription Factors
Sox2 protein, mouse
enhanced green fluorescent protein
Green Fluorescent Proteins
Polycomb Repressive Complex 1

Grants and funding

DP1 DA039562/DA/NIDA NIH HHS/United States