Abstract
There are two physical processes that influence the spatial distribution of transcription factor molecules entering the nucleus of a eukaryotic cell, the binding to genomic DNA and the diffusion throughout the nuclear volume. Comparison of the DNA-protein association rate constant and the protein diffusion constant may determine which one is the limiting factor. If the process is diffusion-limited, transcription factor molecules are captured by DNA before their even distribution in the nuclear volume. Otherwise, if the reaction rate is limiting, these molecules diffuse evenly and then find their binding sites. Using well-studied human NF-κB dimer as an example, we calculated its diffusion constant using the Debye-Smoluchowski equation. The value of diffusion constant was about 10−15 cm3/s, and it was comparable to the NF-κB association rate constant for DNA binding known from previous studies. Thus, both diffusion and DNA binding play an equally important role in NF-κB spatial distribution. The importance of genome 3D-structure in gene expression regulation and possible dependence of gene expression on the local concentration of open chromatin can be hypothesized from our theoretical estimate.
Similar content being viewed by others
Abbreviations
- NF-κB:
-
nuclear factor κB (nuclear factor kappa-light-chain-enhancer of activated B cells)
- TF:
-
transcription factor
References
Kao-Huang, Y., Revzin, A., Butler, A. P., O’Conner, P., Noble, D. W., and von Hippel, P. H. (1977) Proc. Natl. Acad. Sci. USA, 74, 4228–4232.
Elf, J., Li, G.-W., and Xie, X. S. (2007) Science, 316, 1191–1194.
Phair, R. D., Scaffidi, P., Elbi, C., Vecerova, J., Dey, A., Ozato, K., Brown, D. T., Hager, G., Bustin, M., and Misteli, T. (2004) Mol. Cell. Biol., 24, 6393–6402.
Berg, O. G., and von Hippel, P. H. (1985) Annu. Rev. Biophys. Biophys. Chem., 14, 131–160.
Lieberman-Aiden, E., van Berkum, N. L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B. R., Sabo, P. J., Dorschner, M. O., Sandstrom, R., Bernstein, B., Bender, M. A., Groudine, M., Gnirke, A., Stamatoyannopoulos, J., Mirny, L. A., Lander, E. S., and Dekker, J. (2009) Science, 326, 289–293.
Natoli, G., Saccani, S., Bosisio, D., and Marazzi, I. (2005) Nat. Immunol., 6, 439–445.
Bergqvist, S., Alverdi, V., Mengel, B., Hoffmann, A., Ghosh, G., and Komives, E. A. (2009) Proc. Natl. Acad. Sci. USA, 106, 19328–19333.
Case, F., and Alexandridis, P. (2003) Mesoscale Phenomena in Fluid Systems, American Chemical Society, Washington, DC.
Seksek, O., Biwersi, J., and Verkman, A. S. (1997) J. Cell Biol., 138, 131–142.
Siebrasse, J. P., Veith, R., Dobay, A., Leonhardt, H., Daneholt, B., and Kubitscheck, U. (2008) Proc. Natl. Acad. Sci. USA, 105, 20291–20296.
Riggs, A. D., Bourgeois, S., and Cohn, M. (1970) J. Mol. Biol., 53, 401–417.
Tafvizi, A., Huang, F., Fersht, A. R., Mirny, L. A., and van Oijen, A. M. (2011) Proc. Natl. Acad. Sci. USA, 108, 563–568.
Vukojevic, V., Papadopoulos, D. K., Terenius, L., Gehring, W. J., and Rigler, R. (2010) Proc. Natl. Acad. Sci. USA, 107, 4093–4098.
Babayeva, N. D., Wilder, P. J., Shiina, M., Mino, K., Desler, M., Ogata, K., Rizzino, A., and Tahirov, T. H. (2010) Cell Cycle, 9, 3054–3062.
Bolzer, A., Kreth, G., Solovei, I., Koehler, D., Saracoglu, K., Fauth, C., Muller, S., Eils, R., Cremer, C., Speicher, M. R., and Cremer, T. (2005) PLoS Biol., 3, e157.
Marti-Renom, M. A., and Mirny, L. A. (2011) PLoS Comput. Biol., 7, e1002125.
Michalak, P. (2008) Genomics, 91, 243–248.
Khrameeva, E. E., Mironov, A. A., Fedonin, G. G., Khaitovich, P., and Gelfand, M. S. (2012) PLoS One, 7, e33947.
Erdel, F., Muller-Ott, K., Baum, M., Wachsmuth, M., and Rippe K. (2011) Chromosome Res., 19, 99–115.
Mokry, M., Hatzis, P., Schuijers, J., Lansu, N., Ruzius, F. P., Clevers, H., and Cuppen, E. (2012) Nucleic Acids Res., 40, 148–158.
Author information
Authors and Affiliations
Corresponding author
Additional information
Published in Russian in Biokhimiya, 2014, Vol. 79, No. 6, pp. 732–736.
Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM14-042, April 13, 2014.
Rights and permissions
About this article
Cite this article
Sycheva, A.M., Kel, A., Nikolaev, E.N. et al. Equal impact of diffusion and DNA binding rates on the potential spatial distribution of nuclear factor κB transcription factor inside the nucleus. Biochemistry Moscow 79, 577–580 (2014). https://doi.org/10.1134/S0006297914060121
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0006297914060121