Dobi A, v Agoston D
Molecular Control of Neurodifferentiation, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 1998 May 26;95(11):5981-6. doi: 10.1073/pnas.95.11.5981.
Submillimolar levels of calcium, similar to the physiological total (bound + free) intranuclear concentration (0.01-1 mM), induced a conformational change within d(TG/AC)n, one of the frequent dinucleotide repeats of the mammalian genome. This change is calcium-specific, because no other tested cation induced it and it was detected as a concentration-dependent transition from B- to a non-B-DNA conformation expanding from 3' end toward the 5' of the repeat. Genomic footprinting of various rat brain regions revealed the existence of similar non-B-DNA conformation within a d(TG/AC)28 repeat of the endogenous enkephalin gene only in enkephalin-expressing caudate nucleus and not in the nonexpressing thalamus. Binding assays demonstrated that DNA could bind calcium and can compete with calmodulin for calcium.
亚毫摩尔水平的钙，类似于生理状态下细胞核内总的（结合的 + 游离的）钙浓度（0.01 - 1 mM），可诱导d(TG/AC)n发生构象变化，d(TG/AC)n是哺乳动物基因组中常见的二核苷酸重复序列之一。这种变化具有钙特异性，因为其他测试的阳离子均未诱导该变化，并且它被检测为一种浓度依赖性转变，即从B型DNA构象转变为从重复序列的3'端向5'端扩展的非B型DNA构象。对大鼠不同脑区的基因组足迹分析表明，仅在内源性脑啡肽基因的d(TG/AC)28重复序列中，在表达脑啡肽的尾状核而非不表达脑啡肽的丘脑中存在类似的非B型DNA构象。结合实验表明，DNA能够结合钙，并且可以与钙调蛋白竞争钙。
