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Current Topics in Biochemical Research   Volumes    Volume 18 
Abstract
Irreversible creation of chromatin structure plasticity of proximal 5’-upstream regions of Pax5, Aiolos, EBF1 and OBF1 genes with epigenetic modifications to exclude IgM H- and L-chains accumulated in individual clones of HDAC2(-/-) DT40 mutants through various generations during continuous cultivation
Masami Nakayama, Tatsuo Nakayama
Pages: 33 - 56
Number of pages: 24
Current Topics in Biochemical Research
Volume 18 

Copyright © 2017 Research Trends. All rights reserved

ABSTRACT
 
We recently studied acetylation levels of Lys-9, Lys-14, Lys-18, Lys-23 and Lys-27 residues of histone H3 surrounding ~2.0 kb 5’-upstream chromatin regions of Pax5, Aiolos, EBF1 and OBF1 genes in four clones (cl.2-1, cl.2-2, cl.2-4 and cl.2-6) of chicken histone deacetylase2 (HDAC2)-deficient DT40 mutants HDAC2(-/-) during continuous cultivation. In this article, we review our studies on alterations in acetylation levels of these specific Lys residues of histone H3 at the early, middle and later cultivation stages. Acetylation levels of the Lys residues of the four genes were high in DT40 cells. In clone cl.2-1, acetylation levels of one or more of the Lys residues of Pax5, Aiolos and EBF1 genes were dramatically decreased at the early stage and thereafter remained unchanged until the later stage, and those of the OBF1 gene were drastically decreased until the later stage. In clones cl.2-2 and cl.2-4, acetylation levels of Pax5, Aiolos and EBF1 genes were dramatically decreased at the early stage, and thereafter those of the first two were increased until the later stage but those of the last one remained unchanged. In clone cl.2-6, acetylation levels of Pax5, Aiolos and EBF1 genes were drastically decreased at the early stage and thereafter increased until the later stage. These results could explain the previously mentioned ways for varied gene expressions of Pax5, Aiolos, EBF1 and OBF1 in individual HDAC2(-/-) clones during cultivation. We propose a hypothesis concerning distinct ways to gain new cell function to eliminate IgM H- and L-chains accumulated in individual HDAC2(-/-) clones during cultivation. They have an ability to adapt themselves to new environments through irreversible creation of chromatin structure plasticity caused by successive structural changes between tight and loose forms depending on hypo- and hyper-acetylation levels of specific Lys residues of histone H3 surrounding proximal ~2.0 kb 5’-upstream chromatin regions of corresponding genes through various generations, indicating that DT40 cells are pluripotent, elastic and flexible to gain new cell function, attributed to alterations in the chromatin structure.
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