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PDBsum entry 5l0m
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Transcription/DNA
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PDB id
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5l0m
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References listed in PDB file
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Key reference
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Title
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A structural investigation into oct4 regulation by orphan nuclear receptors, Germ cell nuclear factor (gcnf), And liver receptor homolog-1 (lrh-1).
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Authors
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E.R.Weikum,
M.L.Tuntland,
M.N.Murphy,
E.A.Ortlund.
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Ref.
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J Mol Biol, 2016,
428,
4981-4992.
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PubMed id
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Abstract
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Oct4 is a transcription factor required for maintaining pluripotency and
self-renewal in stem cells. Prior to differentiation, Oct4 must be silenced to
allow for the development of the three germ layers in the developing embryo.
This fine-tuning is controlled by the nuclear receptors (NRs), liver receptor
homolog-1 (LRH-1) and germ cell nuclear factor (GCNF). Liver receptor homolog-1
is responsible for driving the expression of Oct4 where GCNF represses its
expression upon differentiation. Both receptors bind to a DR0 motif located
within the Oct4 promoter. Here, we present the first structure of mouse GCNF
DNA-binding domain in complex with the Oct4 DR0. The overall structure revealed
two molecules bound in a head-to-tail fashion on opposite sides of the DNA.
Additionally, we solved the structure of the human LRH-1 DNA-binding domain
bound to the same element. We explore the structural elements that govern Oct4
recognition by these two NRs.
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