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

Publication date: Available online 18 August 2016 Source:Stem Cell Reports Author(s): Jonathan B. Olsen, Loksum Wong, Steven Deimling, Amanda Miles, Hongbo Guo, Yue Li, Zhaolei Zhang, Jack F. Greenblatt, Andrew Emili, Vincent Tropepe 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. Teaser In this article, Tropepe, Emili, and colleagues show...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research