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Two binding sites for thyroid transcription factor 1 (TTF-1) determine the activity of the bovine thyroglobulin gene upstream enhancer element.

Abstract：

:A thyroid-specific enhancer element located upstream from the bovine thyroglobulin gene had been shown to contain three contiguous regions that are protected by thyroid transcription factor 1 (TTF-1) in footprinting experiments in vitro. The functional relevance of the individual TTF-1 binding sites was investigated in a transient assay in primary cultured thyrocytes. Using reporter constructs containing synthetic oligonucleotides overlapping the protected sequences we were able to show that only two out of the three TTF-1 binding sites exhibit transcription enhancing activity. Within the context of the complete enhancer sequence, the central 'inactive' TTF-1 site could be deleted whithout any consequence on the activity of the enhancer in the assay, whereas the presence of both terminal 'active' TTF-1 sites had previously been shown to be strictly required for enhancer function. Our results thus show that the activity of the bovine thyroglobulin upstream enhancer relies on the presence of a pair of TTF-1 binding sites separated by about 30 bp. These results also emphasize the need to assess experimentally the functional relevance of TTF-1 binding sites identified in footprinting experiments.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Christophe-Hobertus C,Christophe D

doi

10.1016/s0303-7207(98)00250-0

keywords:

subject

Has Abstract

pub_date

1999-03-25 00:00:00

pages

79-84

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(98)00250-0

journal_volume

149

pub_type

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