NUCLEASE SENSITIVITY OF THE HUMAN GROWTH HORMONE-CHORIONIC SOMATOMAMMOTROPIN LOCUS IN PITUITARY AND PLACENTA SUGGEST DIFFERENT MECHANISMS FOR TISSUE-SPECIFIC REGULATION

The five human growth hormone (GH) and chorionic somatomammotropin (CS ) genes are located at a single locus on chromosome 17. These genes sh are extensive nucleotide sequence similarity (similar to 94%) even in their flanking DNA, yet GH-N is expressed efficiently in the pituitary under the control of the pituitary-specific factor GHF-1/Pit-1 and th e remaining CS-A, CS-B, CS-L and GH-V genes are transcriptionally acti ve in the placenta. Despite this specificity in vivo, a truncated CS-A promoter can bind GHF-1/Pit-1 and allow CS-A promoter activity in pit uitary cells ill vitro, With a view to assessing whether the placental genes of the GH/CS locus possess a different chromatin structure in t he pituitary and are, thus, less transcriptionally active than the GH- N gene, we have compared the DNAase I sensitivity of GH/CS in isolated pituitary and placenta cell nuclei. Our data indicate that these gene s are equally sensitive in isolated human pituitary nuclei. By contras t, the CS-A? CS-B and CS-L genes were significantly (P < 0.05) more se nsitive than the GH-N gene in isolated human placenta nuclei. Although just not significant, the GH-V gene was slightly more sensitive than the GH-N gene. This pattern was also seen with nuclei from human chori ocarcinoma BeWo and JEG-3 cells, which express low and extremely low l evels of CS RNA, respectively, but was distinct from the pattern obser ved in the non placental human cervical carcinoma HeLa cell line. Thes e data indicate that the inactivity of the CS genes in the pituitary d oes not correlate with a 'closed' chromatin structure. However, they a re consistent with ii role for a more 'open' chromatin conformation in placenta-specific expression, but not necessarily high levels of tran scriptional activity.