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Journal of Lipid Research, Vol 36, 1586-1594, Copyright © 1995 by Lipid Research, Inc.

ARTICLES

Thyroid hormone influences conditional transcript elongation of the apolipoprotein A-I gene in rat liver

YC Lin-Lee, SM Soyal, A Surguchov, S Sanders, W Strobl and W Patsch
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

Chronic administration of thyroid hormone (T3) increases apoA-I gene expression in rat liver by enhancing mRNA maturation, but reduces apoA- I mRNA synthesis to 50% of control. To gain insight into the inverse relation of mRNA maturation and mRNA synthesis, we measured transcription in livers of control and T3-treated rats (50 micrograms/100 g body weight for 7 days) by nuclear run-on assays using overlapping antisense RNA probes encompassing the apoA-I gene. In control rats, after normalization for hybridization efficiency and probe length, the hybridization signals with intron 3 probes were reduced to 45% of those obtained with exon 1 to exon 3 probes (P < 0.01) indicating transcriptional arrest or pausing close to the exon 3- intron 3 border or 450 to 650 nucleotides downstream of the transcription start site. In T3-treated rats, the elongation block was nearly twice as effective, while the rate of transcription initiation was similar to control. In contrast, the distribution of nascent transcripts across the apoA-IV gene was symmetric, and T3-treatment suppressed apoA-IV mRNA synthesis by processes operating in the 5' region such as transcription initiation. Thus, conditional transcript elongation contributes to the regulation of apoA-I gene expression in rat liver.
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