Chromatin structure, transcription, and methylation of the prolactin gene domain in pituitary tumors of Fischer 344 rats.

In order to study prolactin gene transcription and chromatin structure in a relatively homogeneous population of prolactin-producing cells, we induced lactotroph proliferation (pituitary tumor formation) in Fischer 344 rats by chronic diethylstibestrol treatment. We show that the prolactin gene is highly sensitive to digestion by DNase I in the chromatin of these pituitary tumors but not in liver. Furthermore, sequences immediately flanking the prolactin gene exhibit a similar high DNase I sensitivity. This contrasts with previous reports that the coding region of some genes is highly sensitive to DNase I digestion and that adjacent noncoding regions exhibit an intermediate sensitivity. This high level of DNase I sensitivity in the flanking regions was not due to transcription; we did not detect RNA transcripts homologous to any unique DNA sequence within 12 kilobase pairs upstream or downstream of the prolactin gene. We have identified two DNase I-hypersensitive sites 5' to the prolactin gene in pituitary tumors but none in liver. Also, the coding region, but not adjacent noncoding regions, of the prolactin gene domain is hypomethylated at MspI/HpaII and HhaI restriction enzyme sites in pituitary tumors. The prolactin gene domain is methylated at these sites in liver.