RGD Reference Report - Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers. - Rat Genome Database

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Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers.

Authors: Remenyi, A  Lins, K  Nissen, LJ  Reinbold, R  Scholer, HR  Wilmanns, M 
Citation: Remenyi A, etal., Genes Dev 2003 Aug 15;17(16):2048-59.
RGD ID: 1549851
Pubmed: PMID:12923055   (View Abstract at PubMed)
PMCID: PMC196258   (View Article at PubMed Central)
DOI: DOI:10.1101/gad.269303   (Journal Full-text)

Members of the POU and SOX transcription factor families exemplify the partnerships established between various transcriptional regulators during early embryonic development. Although functional cooperativity between key regulator proteins is pivotal for milestone decisions in mammalian development, little is known about the underlying molecular mechanisms. In this study, we focus on two transcription factors, Oct4 and Sox2, as their combination on DNA is considered to direct the establishment of the first three lineages in the mammalian embryo. Using experimental high-resolution structure determination, followed by model building and experimental validation, we found that Oct4 and Sox2 were able to dimerize onto DNA in distinct conformational arrangements. We demonstrate that the DNA enhancer region of their target genes is responsible for the correct spatial alignment of glue-like interaction domains on their surface. Interestingly, these surfaces frequently have redundant functions and are instrumental in recruiting various interacting protein partners.

Objects referenced in this article
Gene Pou5f1 POU class 5 homeobox 1 Rattus norvegicus

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