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Current Topics in Biochemical Research   Volumes    Volume 22 
Abstract
A comprehensive review on the chromatin conformation change code (4C) theory: A theory on ways of higher eukaryotes to gain un-programmed and new cell functions by means of irreversible creation of chromatin structure plasticity with epigenetic modifications through numerous generations
Tatsuo Nakayama, Masami Nakayama
Pages: 43 - 90
Number of pages: 48
Current Topics in Biochemical Research
Volume 22 

Copyright © 2021 Research Trends. All rights reserved

ABSTRACT
 
In this article we first reviewed our studies on the exclusion of a large amount of IgM H- and L-chains excessively accumulated in histone deacetylase2 (HDAC2)-deficient DT40 mutants HDAC2(-/-) during continuous cultivation as a concrete case. Based on these results, we proposed a universal hypothetic concept on the ability of higher eukaryotes for gaining un-programmed and new cell function(s), originally based on the pluri-potency, elasticity and flexibility of the chromatin structure, in order to cope with and/or overcome new environment change. We named the remarkable bio-system the chromatin conformation change code (4C) theory. Outline of the 4C theory is concretely as follows. Somatic cells of higher eukaryotes gradually acquire un-programmed and new cell functions to cope with and/or overcome environment change, by means of creation of chromatin structure plasticity surrounding proximal 5’-upstream regions of specific transcription factor and chromatin-modifying enzyme genes with epigenetic modifications through numerous generations. Creation of chromatin structure plasticity in individual somatic cells of the same type is triggered by spontaneous unbalanced response to the environment change, followed irreversibly and diversely by its successive convergence, and accomplished in descendent cells but not in the cell which initially meets with the environment change. The environment change is recognized by putative environment change recognition receptor/site (ECRR/ECRS), and chromatin structure plasticity is irreversibly and directly created by putative chromatin conformation change complex (4C) machinery. The chromatin structure of the proximal 5’-upstream region(s) of the specific gene(s) receives the signal on the environment change, and directs the switch (on or off) for its gene expression ability through alterations between loose and tight forms. The number of codes in the 4C theory, which determines diverse cell functions and types, may be determined by the multiplication of the number of candidate genes and that (probably two) of codes for each of candidate genes.
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