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

Autor: Jonathan B. Olsen, Loksum Wong, Steven Deimling, Amanda Miles, Hongbo Guo, Yue Li, Zhaolei Zhang, Jack F. Greenblatt, Andrew Emili, Vincent Tropepe
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Stem Cell Reports, Vol 7, Iss 3, Pp 454-470 (2016)
Druh dokumentu: article
ISSN: 2213-6711
DOI: 10.1016/j.stemcr.2016.06.012
Popis: 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.
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