| Co-Investigator(Kenkyū-buntansha) |
BUERSTEDDE J ハンブルグ大学, 教授
TAKEDA Shunichi Kyoto University, Faculty of Medicine, Professor, 大学院・医学研究科, 教授 (60188191)
KIKUCHI Hidehiko Miyazaki Medical College, Assistant Professor, 医学部, 助手 (10301384)
TAKECHI Shinji Miyazaki Medical College, Assistant Professor, 医学部, 助手 (10222100)
TAKAMI Yasunari Miyazaki Medical College, Associate Professor, 医学部, 講師 (80236356)
JEAN-MARIE Buerstedde Hamburg University, Professor
BUEROTEDLE U ハンブルク大学, 教授
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| Budget Amount *help |
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1998: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1997: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Research Abstract |
Thirty-nine of the 44 chicken H1 and core histone genes are located in a major histone gene cluster of 110 kb. In this study, using gene targeting techniques, we generated several DT4O mutants, respectively, which are devoid of one or two particular histone genes, one allele of the major gene cluster of 110 kb, an approximately 57 kb segment of the cluster carrying 21 genes, and 11 of the 12 H1 gene copies. Systematic analyses of the resultant mutants led us to some noticeable conclusions, as follows.
1)All of the histone gene families have the inherent ability to compensate for the deletion of approximately half of their own constituents, and to maintain the amount of each of the histone subtypes in stoichiometric balance, based on increases in the expression of the remaining genes, regardless of the complete disruption of one allele of the major gene cluster or the disruption of approximately half segments of the two alleles. Therefore, one allele of the major histone gene cluster is enough for cell proliferation.
2)The deletion of 11 of the 12 H1 gene copies does not affect cell functions, i.e. the growth rate and global chromatin structure. These results indicate that only one copy of the H1 genes is enough for cell proliferation.
3)The protein patterns are not altered in the case of the deletion of one allele of the cluster, due to no changes in the composition of any histone variant, but vary in the case of the deletion of approximately half segments of the cluster, and the latter plus more Hl gene(s), due to changes in the quality of the H1 and core variants.
4)The protein patterns are altered in the mutants, respectively, lacking particular Hl and H2B variants. The variable proteins are specific for the corresponding mutants, suggesting that the H1 and core variants should be individually involved in regulation of the expression of specific genes, through alterations in the chrornatin structure localized in specific genomic regions.
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