TRANSCRIPTION OF THE HUMAN CORTICOTROPIN-RELEASING HORMONE GENE IN NPLC CELLS IS CORRELATED WITH Z-DNA FORMATION

The intron of the corticotropin-releasing hormone (corticoliberin; CRH ) gene contains a sequence of over 100 bp of alternating purine/pyrimi dine residues, We have used binding of a Z-DNA-specific antibody in me tabolically active, permeabilized nuclei to study the formation of Z-D NA in this sequence at various levels of transcription, In the NPLC hu man primary liver carcinoma cell line, activation of cAMP-dependent pa thways increased the level of transcription, while adding glucocortico ids inhibited transcription of the CRH gene, These cells respond in a manner similar to hypothalamic cells, Z-DNA formation in this sequence was detected at the basal level of transcription, as well as after st imulation with forskolin, Inhibition of transcription by dexamethasone abolished Z-DNA formation, Z-DNA formation in the MYC gene (c-myc) wa s affected differently in the same experiment, Thus, changes in Z-DNA formation in the CRH gene are gene specific and are linked to the tran scription of the gene.