Format

Send to

Choose Destination
Stem Cell Reports. 2016 Sep 13;7(3):454-470. doi: 10.1016/j.stemcr.2016.06.012. Epub 2016 Aug 18.

G9a and ZNF644 Physically Associate to Suppress Progenitor Gene Expression during Neurogenesis.

Author information

1
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Medical Science Building, Toronto, ON M5S 3E1, Canada.
2
Department of Cell and Systems Biology, University of Toronto, Toronto, ON, M5S 3G5, Canada.
3
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.
4
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Medical Science Building, Toronto, ON M5S 3E1, Canada; Department of Computer Science, University of Toronto, Toronto, ON M5S 3G4, Canada.
5
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Medical Science Building, Toronto, ON M5S 3E1, Canada. Electronic address: andrew.emili@utoronto.ca.
6
Department of Cell and Systems Biology, University of Toronto, Toronto, ON, M5S 3G5, Canada; Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON M5T 3A9, Canada; Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, ON M5S 3B2, Canada. Electronic address: v.tropepe@utoronto.ca.

Abstract

Proliferating progenitor cells undergo changes in competence to give rise to post-mitotic progeny of specialized function. These cell-fate transitions typically involve dynamic regulation of gene expression by histone methyltransferase (HMT) complexes. However, the composition, roles, and regulation of these assemblies in regulating cell-fate decisions in vivo are poorly understood. Using unbiased affinity purification and mass spectrometry, we identified the uncharacterized C2H2-like zinc finger protein ZNF644 as a G9a/GLP-interacting protein and co-regulator of histone methylation. In zebrafish, functional characterization of ZNF644 orthologs, znf644a and znf644b, revealed complementary roles in regulating G9a/H3K9me2-mediated gene silencing during neurogenesis. The non-overlapping requirements for znf644a and znf644b during retinal differentiation demarcate critical aspects of retinal differentiation programs regulated by differential G9a-ZNF644 associations, such as transitioning proliferating progenitor cells toward differentiation. Collectively, our data point to ZNF644 as a critical co-regulator of G9a/H3K9me2-mediated gene silencing during neuronal differentiation.

PMID:
27546533
PMCID:
PMC5031922
DOI:
10.1016/j.stemcr.2016.06.012
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center