Transcription of the human corticotropin-releasing hormone gene in NPLC cells is correlated with Z-DNA formation.

• DOI: 10.1073/pnas.93.8.3664
• Publication Date: 2002-07-26T14:35:07Z
• Authors: S Wölfl; C Martinez; A Rich; J A Majzoub
• Keywords: 0303 health sciences; Base Sequence; Transcription, Genetic; Corticotropin-Releasing Hormone; Molecular Sequence Data; Genes, myc; DNA; Introns; Cell Line; 3. Good health; 03 medical and health sciences; Gene Expression Regulation; Humans; DNA Primers

The intron of the corticotropin-releasing hormone (corticoliberin; CRH) gene contains a sequence of over 100 bp of alternating purine/pyrimidine residues. We have used binding of a Z-DNA-specific antibody in metabolically active, permeabilized nuclei to study the formation of Z-DNA in this sequence at various levels of transcription. In the NPLC human primary liver carcinoma cell line, activation of cAMP-dependent pathways increased the level of transcription, while adding glucocorticoids 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 stimulation with forskolin. Inhibition of transcription by dexamethasone abolished Z-DNA formation. Z-DNA formation in the WC gene (c-myc) was affected differently in the same experiment. Thus, changes in Z-DNA formation in the CRH gene are gene specific and are linked to the transcription of the gene.