PUBLICATION

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

Authors
Olsen, J.B., Wong, L., Deimling, S., Miles, A., Guo, H., Li, Y., Zhang, Z., Greenblatt, J.F., Emili, A., Tropepe, V.
ID
ZDB-PUB-160823-4
Date
2016
Source
Stem Cell Reports   7(3): 454-70 (Journal)
Registered Authors
Li, Yue, Tropepe, Vincent, Wong, Loksum
Keywords
none
Datasets
GEO:GSE63225
MeSH Terms
  • Animals
  • Binding Sites
  • Biomarkers
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival/genetics
  • Gene Expression Regulation, Developmental*
  • Gene Silencing
  • Histocompatibility Antigens/genetics
  • Histocompatibility Antigens/metabolism*
  • Histone-Lysine N-Methyltransferase/genetics
  • Histone-Lysine N-Methyltransferase/metabolism*
  • Histones/metabolism
  • Humans
  • Methylation
  • Neural Stem Cells/cytology*
  • Neural Stem Cells/metabolism*
  • Neurogenesis/genetics*
  • Neurons/cytology
  • Neurons/metabolism
  • Phenotype
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Interaction Maps
  • Retina/metabolism
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Zebrafish
PubMed
27546533 Full text @ Stem Cell Reports
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping