ZFIN ID: ZDB-PUB-160823-4
G9a and ZNF644 Physically Associate to Suppress Progenitor Gene Expression during Neurogenesis
Olsen, J.B., Wong, L., Deimling, S., Miles, A., Guo, H., Li, Y., Zhang, Z., Greenblatt, J.F., Emili, A., Tropepe, V.
Date: 2016
Source: Stem Cell Reports   7(3): 454-70 (Journal)
Registered Authors: Li, Yue, Tropepe, Vincent, Wong, Loksum
Keywords: none
Microarrays: 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
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.