Genetic Mechanisms of Age Regulation of Human Blood Coagulation Factor IX

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Science  30 Jul 1999:
Vol. 285, Issue 5428, pp. 739-743
DOI: 10.1126/science.285.5428.739

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Blood coagulation capacity increases with age in healthy individuals. Through extensive longitudinal analyses of human factor IX gene expression in transgenic mice, two essential age-regulatory elements, AE5′ and AE3′, have been identified. These elements are required and together are sufficient for normal age regulation of factor IX expression. AE5′, a PEA-3 related element present in the 5′ upstream region of the gene encoding factor IX, is responsible for age-stable expression of the gene. AE3′, in the middle of the 3′ untranslated region, is responsible for age-associated elevation in messenger RNA levels. In a concerted manner, AE5′ and AE3′ recapitulate natural patterns of the advancing age–associated increase in factor IX gene expression.

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