Changes in transcriptional activity and matrix association of α_2u-globulin gene family in the rat liver during maturation and aging

Hepatic synthesis of α_2u-globulin in the male rat begins at puberty (about 40 days), reaches a peak level at about 80 days, and ceases at about 750-800 days of age. The age-dependent changes in α_2u-globulin synthesis are correlated with both the steady-state level of the hepatic mRNA for this protein and the rate of transcription of the α_2u-globulin gene family. Transcriptional activation of the α_2u-globulin gene family at puberty and cessation of transcription at senescence correlate with the association and dissociation of this gene domain with the nuclear matrix. Unlike the α_2u-globulin gene, the albumin gene in the liver shows preferential association with the nuclear matrix throughout the life. From these results we conclude that the age-dependent changes in α_2u-globulin synthesis are due to the alteration in the rate of transcription of the α_2u-globulin gene, and that the association of this gene domain to the nuclear matrix is a prerequisite to its transcriptional activation.