Molecular basis of cooperative DNA bending and oriented heterodimer binding in the NFAT1—Fos–Jun—ARRE2 complex

Diebold, Ronald J.; Rajaram, Nirmala; Leonard, David A.; Kerppola, Tom K.

doi:10.1073/pnas.95.14.7915

Cited by 38 publications

(50 citation statements)

References 29 publications

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“…The orientation of heterodimer binding at different regulatory elements can vary due to the recognition of flanking DNA sequences or asymmetric base pairs in nonconsensus binding sites as well as through interactions with other DNA binding proteins (1,4,5,15). Because the orientation of heterodimer binding can be reversed without the requirement for dissociation and reassembly of the complex, it can provide a mechanism for rapidly reversible control of transcriptional activity.…”

Section: Discussionmentioning

confidence: 99%

“…Proteins encompassing the bZIP domains of Fos (residues 137-200) and Jun (residues 255-318), with unique cysteine residues at positions 136 and 254, respectively, were expressed as hexahistidine fusion proteins in Escherichia coli and purified (2,15). The bZIP domains were modified to contain unique cysteine residues through replacement of the native cysteines by serines and addition of cysteine residues on the amino terminal sides of the bZIP domains.…”

Section: Methodsmentioning

confidence: 99%

“…NFAT1 can overcome the intrinsic orientation preference of Fos-Jun and reorient the heterodimer at all composite sites examined (1,15). To investigate whether the preferred orientation of heterodimer binding affected the properties of Fos-Jun-NFAT1 complexes subsequent to reorientation, we examined the effects of heterodimer orientation preference on the stabilities and transcriptional activities of Fos-Jun-NFAT1 complexes.…”

Section: Effects Of Heterodimer Orientation Preference On Fos-jun-nfat1mentioning

confidence: 99%

“…The contact interface between Fos-Jun and NFAT1 observed in the Fos-Jun-NFAT1-ARRE2 crystal can only be formed with heterodimers bound in one orientation (14). Heterodimers that are bound in the opposite orientation must be rotated by 180°a bout the dimer axis (1,15). It is not known whether the heterodimer orientation is reversed by dissociation and rebinding of Fos-Jun or through reorientation of the heterodimer in association with DNA.…”

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confidence: 99%

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Dynamics of Fos-Jun-NFAT1 complexes

Ramirez-Carrozzi

Kerppola

2001

Proc. Natl. Acad. Sci. U.S.A.

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Transcription initiation in eukaryotes is controlled by nucleoprotein complexes formed through cooperative interactions among multiple transcription regulatory proteins. These complexes may be assembled via stochastic collisions or defined pathways. We investigated the dynamics of Fos-Jun-NFAT1 complexes by using a multicolor fluorescence resonance energy transfer assay. Fos-Jun heterodimers can bind to AP-1 sites in two opposite orientations, only one of which is populated in mature Fos-Jun-NFAT1 complexes. We studied the reversal of Fos-Jun binding orientation in response to NFAT1 by measuring the efficiencies of energy transfer from donor fluorophores linked to opposite ends of an oligonucleotide to an acceptor fluorophore linked to one subunit of the heterodimer. The reorientation of Fos-Jun by NFAT1 was not inhibited by competitor oligonucleotides or heterodimers. The rate of Fos-Jun reorientation was faster than the rate of heterodimer dissociation at some binding sites. The facilitated reorientation of Fos-Jun heterodimers therefore can enhance the efficiency of Fos-Jun-NFAT1 complex formation. We also examined the influence of the preferred orientation of Fos-Jun binding on the stability and transcriptional activity of Fos-Jun-NFAT1 complexes. Complexes formed at sites where Fos-Jun favored the same binding orientation in the presence and absence of NFAT1 exhibited an 8-fold slower dissociation rate than complexes formed at sites where Fos-Jun favored the opposite binding orientation. Fos-Jun-NFAT1 complexes also exhibited greater transcription activation at promoter elements that favored the same orientation of Fos-Jun binding in the presence and absence of NFAT1. Thus, the orientation of heterodimer binding can influence both the dynamics and promoter selectivity of multiprotein transcription regulatory complexes.M any transcription regulatory proteins form heterodimers that bind to palindromic DNA sequences. Such heterodimers can potentially bind their recognition sites in either of two opposite orientations (1-5). Heterodimers that bind in opposite orientations present different protein surfaces for interactions with adjacent DNA binding proteins. Thus, the orientation of heterodimer binding may influence interactions with other transcription factors. Opposite orientations of heterodimer binding can result in different transcriptional activities (6-9). The mechanisms whereby the orientation of heterodimer binding controls transcriptional activity have not been defined.Fos and Jun family basic region-leucine zipper (bZIP) proteins regulate the expression of different genes in different cell types through cooperative interactions with other transcription factor families (10). Complexes formed by Fos and Jun with members of the NFAT family at composite regulatory elements induce cytokine gene expression in T cells activated by antigen presentation (11,12). The x-ray crystal structures of DNA-bound complexes formed by the bZIP domains of Fos and Jun alone as well as by the DNA binding domains of Fos, Jun...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Effects Of Heterodimer Orientation Preference On Fos-jun-nfat1mentioning

confidence: 99%

mentioning

confidence: 99%

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Dynamics of Fos-Jun-NFAT1 complexes

Ramirez-Carrozzi

Kerppola

2001

Proc. Natl. Acad. Sci. U.S.A.

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“…Interactions between such heterodimers and transcription factors that bind adjoining sequences are generally thought to require a specific orientation of heterodimer binding. For instance, cooperative DNA binding by Fos-Jun, Fos-Activating Transcription Factor 2 (ATF2), 2 or ATF2-Jun heterodimers with Nuclear Factor of Activated T cells 1 (NFAT1) at composite regulatory elements imposes a fixed orientation of heterodimer binding (3)(4)(5)(6)(7). Differences in the preferred orientation of Fos-Jun heterodimer binding at different regulatory elements affect cooperative DNA binding and synergistic transcription activation with NFAT1 (6 -8).…”

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confidence: 99%

Opposite Orientations of a Transcription Factor Heterodimer Bind DNA Cooperatively with Interaction Partners but Have Different Effects on Interferon-β Gene Transcription

Burns

Kerppola

2012

Journal of Biological Chemistry

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Background: Nucleoprotein complexes are frequently assumed to adopt a unique configuration. Results: ATF2-Jun heterodimers bound the interferon-␤ enhancer in two opposite orientations in association with IRF3 and HMGI. Opposite heterodimer orientations exhibited the same cooperativity of ATF2-Jun-IRF3-HMGI complex formation, but had distinct transcriptional activities. Conclusion: ATF2-Jun heterodimer orientation did not affect binding cooperativity, but affected transcriptional activity. Significance: Changes in transcription complex configuration can regulate transcriptional activity.

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Quantitative distance information on protein-DNA complexes determined in polyacrylamide gels by fluorescence resonance energy transfer

Lorenz¹,

Diekmann²

2001

Electrophoresis

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In polyacrylamide gels, we have quantitatively determined Forster transfer (fluorescense resonance energy transfer, FRET) between two fluorescent dyes attached to DNA in protein-DNA complexes. The donor-dye fluorescein labeled to DNA retains its free mobility in the polyacrylamide gel, however, its fluorescence properties change. The different quantum yield of fluorescein in the gel is found to be independent of the gel concentration and can thus be quantitatively taken into account by a reduced Forster distance R0 of 46 A compared to 50 A in solution. We have determined global structural properties of two proteins binding to double-labeled DNA using a novel gel-based fluorescence resonance energy transfer assay. In polyacrylamide gels we have analyzed the binding of integration host factor (IHF) and the high mobility group protein NHP6a to their substrate DNA. The measured Forster transfer efficiency allows us to deduce information on the overall shape and the DNA bending angle in the complex.

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Molecular basis of cooperative DNA bending and oriented heterodimer binding in the NFAT1—Fos–Jun—ARRE2 complex

Cited by 38 publications

References 29 publications

Dynamics of Fos-Jun-NFAT1 complexes

Dynamics of Fos-Jun-NFAT1 complexes

Opposite Orientations of a Transcription Factor Heterodimer Bind DNA Cooperatively with Interaction Partners but Have Different Effects on Interferon-β Gene Transcription

Quantitative distance information on protein-DNA complexes determined in polyacrylamide gels by fluorescence resonance energy transfer

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