PHYSICAL LINKAGE OF THE HUMAN GROWTH-HORMONE GENE FAMILY AND THE THYROID-HORMONE RECEPTOR INTERACTING PROTEIN-1 GENE ON CHROMOSOME-17

A P1 cloned insert of about 85.5 kilobases (kb) was isolated, containi ng four members of the human growth hormone/chorionic somatomammotropi n (GH/CS) gene family and the thyroid hormone receptor interacting pro tein (TRIP-1) gene. The presence of the CS-like, CS-A, GH-variant and, most downstream, CS-B gene was confirmed by DNA blotting and sequence analysis. The TRIP-1 gene was detected 40 kb downstream of the CS-B g ene and in the reverse transcriptional orientation to all the GH/CS ge nes. The TRIP-1 gene is highly homologous to the SUG-1 gene in yeast a nd is evolutionarily conserved among several species. Based on the com mon location of the GH and TRIP-1 (or homologue) genes on the same chr omosome in the human, pig and rat genomes, we suggest that these loci are physically linked. Previously, it was reported that a muscle-speci fic sodium channel (SCN4A) gene is located immediately upstream of the pituitary growth hormone (GH-N) gene, and is linked to the GH gene lo cus in both humans and rats. This suggests a further linkage between t he SCN4A, GH and TRIP-1 loci. Also, deoxyribonuclease hypersensitive s ites have been reported in and around these loci and were associated w ith an important locus control region for the GH/CS genes. Unlike the GH/CS genes, we show, using reverse transcriptase-polymerase chain rea ction that the TRIP-1 gene is expressed ubiquitously and, through RNA blotting, as a 1.4-kb transcript. This implies an open and active chro matin structure. The possible effect of this structure on the adjacent human GH/CS gene locus is discussed. (C) 1998 Elsevier Science B.V. A ll rights reserved.