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1 Laboratory of Developmental Biology, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
2 Biomedicinal Information Research Center (BIRC), National Institute of Advanced Industrial Science and Technology (AIST), 2-42 Aomi, Koto-ku, Tokyo 135-0064, Japan
A rapid increase in research on the relationship between histone modifications and their subsequent reactions in the nucleus has revealed that the histone modification system is complex, and robust against point mutations. The prevailing theoretical framework (the histone code hypothesis) is inadequate to explain either the complexity or robustness, making the formulation of a new theoretical framework both necessary and desirable. Here, we develop a model of the regulatory network of histone modifications in which we encode histone modifications as nodes and regulatory interactions between histone modifications as links. This network has scale-free properties and subnetworks with a pseudo–mirror symmetry structure, which supports the robustness of the histone modification network. In addition, we show that the unstructured tail regions of histones are suitable for the acquisition of this scale-free property. Our model and related insights provide the first framework for an overall architecture of a histone modification network system, particularly with regard to the structural and functional roles of the unstructured histone tail region. In general, the post-translational "modification webs" of natively unfolded regions (proteins) may function as signal routers for the robust processing of the large amounts of signaling information.
These authors contributed equally to the work.
* Correspondence: horikosh{at}iam.u-tokyo.ac.jpThis article has been cited by other articles:
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M. Sakamoto, S. Noguchi, S. Kawashima, Y. Okada, T. Enomoto, M. Seki, and M. Horikoshi Global analysis of mutual interaction surfaces of nucleosomes with comprehensive point mutants Genes Cells, November 1, 2009; 14(11): 1271 - 1330. [Abstract] [Full Text] [PDF] |
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