Identification of a thyroid-specific and cAMP-responsive enhancer in the upstream sequences of the human thyroglobulin promoter

摘要

Functional analysis of remote 5' flanking sequences from the huiniin thyroglobulin gene in primary cultured dug thyrocytes led to the identilicniion of a panly cAMI'-responsive enhancer, located between —3.6 to —2.2 kb from the transeriplionui start site. Deletion analysis of the I IvhToni1 lejiimi localised the enhancer activity in i 0.5 kb-long I'nigment (located between — S.2 and — 2.7 kb relative to tniiisiTiplion start), which could be divided into two functional sub-fragments of 0.2 and 03 kb. A potential binding site for the CREB/AT1' liaiiNeiipiioii factor* was found in the 0.3 kb element. The complete enhancer region had no delectable activity when assayed in Helu cells, sui, csiinj that it constituted thyroid-specific regulatory element. Accordingly, fontpriniing experiments revealed the prcsoiice of several bindinsi sites for Thyroid Transcription actor-1 (TTF-I) in both the 0.2 and 0.3 kb elements.