S. Wolfl et al., TRANSCRIPTION OF THE HUMAN CORTICOTROPIN-RELEASING HORMONE GENE IN NPLC CELLS IS CORRELATED WITH Z-DNA FORMATION, Proceedings of the National Academy of Sciences of the United Statesof America, 93(8), 1996, pp. 3664-3668
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.