A thermodynamic model for the agglomeration of DNA-looping proteins

In this paper, we propose a thermodynamic mechanism for the formation of transcriptional foci via the joint agglomeration of DNA-looping proteins and protein binding domains on DNA: the competition between the gain in protein–DNA binding free energy and the entropy loss due to DNA looping is argued to result in an effective attraction between loops. A mean-field approximation can be described analytically via a mapping to a restricted random-graph ensemble having local degree constraints and global constraints on the number of connected components. It shows the emergence of protein clusters containing a finite fraction of all looping proteins. If the entropy loss due to a single DNA loop is high enough, this transition is found to be of first order.

[1]  Hernan G. Garcia,et al.  Transcriptional Regulation by the Numbers 2: Applications , 2004, q-bio/0412011.

[2]  H A Scheraga,et al.  Phase transitions in one dimension and the helix-coil transition in polyamino acids. , 1966, The Journal of chemical physics.

[3]  L. Schulman,et al.  One dimensional 1/|j − i|S percolation models: The existence of a transition forS≦2 , 1986 .

[4]  Michael E. Fisher,et al.  Effect of Excluded Volume on Phase Transitions in Biopolymers , 1966 .

[5]  Leonor Saiz,et al.  DNA looping in gene regulation: from the assembly of macromolecular complexes to the control of transcriptional noise. , 2005, Current opinion in genetics & development.

[6]  T. Cremer,et al.  Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions , 2007, Nature Reviews Genetics.

[7]  Daniel Segrè,et al.  Chromosomal periodicity of evolutionarily conserved gene pairs , 2007, Proceedings of the National Academy of Sciences.

[8]  P. Cook.  The organization of replication and transcription. , 1999, Science.

[9]  Nicolas E. Buchler,et al.  On schemes of combinatorial transcription logic , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[10]  G. Wuite,et al.  How DNA coiling enhances target localization by proteins , 2008, Proceedings of the National Academy of Sciences.

[11]  R. Metzler,et al.  Entropy loss in long-distance DNA looping. , 2002, Biophysical journal.

[12]  Thirumalai,et al.  Internal constraints induce localization in an isolated polymer molecule. , 1996, Physical review letters.

[13]  S. Leibler,et al.  DNA looping and physical constraints on transcription regulation. , 2003, Journal of molecular biology.

[14]  François Képès,et al.  Periodic epi-organization of the yeast genome revealed by the distribution of promoter sites. , 2003, Journal of molecular biology.

[15]  L. Mirny,et al.  How gene order is influenced by the biophysics of transcription regulation , 2007, Proceedings of the National Academy of Sciences.

[16]  Leonor Saiz,et al.  Multiprotein DNA looping. , 2006, Physical review letters.

[17]  Cédric Vaillant,et al.  Transcription-Based Solenoidal Model of Chromosomes , 2004, Complexus.

[18]  R. Monasson,et al.  On Large Deviation Properties of Erdös–Rényi Random Graphs , 2003, cond-mat/0311535.

[19]  T. Cremer,et al.  Chromosome territories, nuclear architecture and gene regulation in mammalian cells , 2001, Nature Reviews Genetics.

[20]  J. Davies,et al.  Molecular Biology of the Cell , 1983, Bristol Medico-Chirurgical Journal.

[21]  J. M. Oshorn.  Proc. Nat. Acad. Sei , 1978 .

[22]  D. Marenduzzo,et al.  Modeling a self-avoiding chromatin loop: relation to the packing problem, action-at-a-distance, and nuclear context. , 2006, Structure.

[23]  Kantor,et al.  Conformations of randomly linked polymers. , 1996, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[24]  C. Micheletti,et al.  Depletion effects and loop formation in self-avoiding polymers. , 2006, Physical review letters.

[25]  L. Peliti,et al.  Why is the DNA denaturation transition first order? , 2000, Physical review letters.

[26]  Peter R. Cook,et al.  Predicting three-dimensional genome structure from transcriptional activity , 2002, Nature Genetics.