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2015 ; 16
(2
): 117-27
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Changing Faces of Transcriptional Regulation Reflected by Zic3
#MMPMID26085810
Winata CL
; Kondrychyn I
; Korzh V
Curr Genomics
2015[Apr]; 16
(2
): 117-27
PMID26085810
show ga
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.