The advent of genomics in the study of developmental mechanisms has brought a trove of information
on gene datasets and regulation during development, where the Zic family of zinc-finger proteins
plays an important role. Genomic analysis of the modes of action of Zic3 in pluripotent cells demonstrated its
requirement for maintenance of stem cells pluripotency upon binding to the proximal regulatory regions
(promoters) of genes associated with cell pluripotency (Nanog, Sox2, Oct4, etc.) as well as cell cycle, proliferation, oncogenesis
and early embryogenesis. In contrast, during gastrulation and neurulation Zic3 acts by binding the distal regulatory
regions (enhancers, etc) associated with control of gene transcription in the Nodal and Wnt signaling pathways, including
genes that act to break body symmetry. This illustrates a general role of Zic3 as a transcriptional regulator that
acts not only alone, but in many instances in conjunction with other transcription factors. The latter is done by binding to
adjacent sites in the context of multi-transcription factor complexes associated with regulatory elements.
Keywords: Enhancer, Gastrulation, Left-right asymmetry, Neurogenesis, Promoter, Stem cells, Transcription, Zebrafish.
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