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PDBsum entry 5bng
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References listed in PDB file
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Key reference
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Title
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Dna-Dependent formation of transcription factor pairs alters their binding specificity.
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Authors
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A.Jolma,
Y.Yin,
K.R.Nitta,
K.Dave,
A.Popov,
M.Taipale,
M.Enge,
T.Kivioja,
E.Morgunova,
J.Taipale.
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Ref.
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Nature, 2015,
527,
384-388.
[DOI no: ]
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PubMed id
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Abstract
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Gene expression is regulated by transcription factors (TFs), proteins that
recognize short DNA sequence motifs. Such sequences are very common in the human
genome, and an important determinant of the specificity of gene expression is
the cooperative binding of multiple TFs to closely located motifs. However,
interactions between DNA-bound TFs have not been systematically characterized.
To identify TF pairs that bind cooperatively to DNA, and to characterize their
spacing and orientation preferences, we have performed consecutive
affinity-purification systematic evolution of ligands by exponential enrichment
(CAP-SELEX) analysis of 9,400 TF-TF-DNA interactions. This analysis revealed 315
TF-TF interactions recognizing 618 heterodimeric motifs, most of which have not
been previously described. The observed cooperativity occurred promiscuously
between TFs from diverse structural families. Structural analysis of the TF
pairs, including a novel crystal structure of MEIS1 and DLX3 bound to their
identified recognition site, revealed that the interactions between the TFs were
predominantly mediated by DNA. Most TF pair sites identified involved a large
overlap between individual TF recognition motifs, and resulted in recognition of
composite sites that were markedly different from the individual TF's motifs.
Together, our results indicate that the DNA molecule commonly plays an active
role in cooperative interactions that define the gene regulatory lexicon.
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