In this article we review our recent studies on the ability of higher eukaryotes to gain un-programmed and new cell functions by means of irreversible creation of chromatin structure plasticity through various generations. Following the exclusion of excessively accumulated IgM H- and L-chains in histone deacetylase2 (HDAC2)-deficient DT40 mutants HDAC2(-/-) as a concrete case, we proposed a universal hypothetic concept on the ability of higher eukaryotic cells to adapt to abnormal environment changes. When higher eukaryotic cells firstly encounter moderate intra- and/or extra-cellular environment change, they acquire the ability to cope with and/or overcome it through irreversible creation of plasticity of the varied chromatin structure surrounding proximal 5’-upstream regions of the specific transcription factor and chromatin-modifying enzyme genes. The basis for this striking biological event is their successive chromatin conformational change with epigenetic modifications through various generations. Putative environment change recognition receptor/site (ECRR/ECRS) recognizes the new environment change. Putative chromatin conformation change complex (4C) machinery irreversibly and separately creates plasticity of the varied chromatin structure surrounding the proximal 5’-upstream regions of the above-mentioned specific factor and enzyme genes in distinct ways in individual cells of the same cell type. We advance a chromatin conformation change code (4C) theory for the bio-system to gain un-programmed and new cell function(s) by means of irreversible creation of chromatin structure plasticity by the 4C machinery through various generations, in order to adapt to the new environment change recognized by ECRR/ECRS. The 4C theory is suitable as an explanation for the ways to control development and differentiation of higher eukaryotes.
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