HOWDESHELL, K.L.; SACHS, L.; DEMENEIX, B.; DENVER, R.J.; Univ. of Michigan, Ann Arbor; Museum National D-Histoire Naturelle, Paris, France; Museum National D-Histoire Naturelle, Paris, France; Univ. of Michigan, Ann Arbor: A Role for Basic Transcription Element Binding Protein (BTEB1) in the Autoinduction of the Xenopus laevis Thyroid Hormone Receptor Beta (TRβ) gene

Basic transcription element binding protein 1 (BTEB1) is a member of the Kr�ppel family of transcription factors. BTEB1 binds to GC-rich regions in gene promoters with high affinity and can activate or repress transcription depending on the architecture of the promoter and/or the cell type. BTEB1 is a thyroid hormone (T3) responsive gene that may be an essential intermediate in T3 action during development. During Xenopus tadpole metamorphosis, BTEB1 mRNA levels rise and can be precociously induced by T3. Thyroid receptor beta (TRβ) mRNA levels rise coincident with BTEB1, and TRβ is autoinduced during metamorphosis. The presence of 7 GC box sequences within the TRβ promoter led us to hypothesize that BTEB1 may participate in the autoinduction of TRβ during tadpole metamorphosis. In gel shift assays, we found that recombinant BTEB1 DNA binding domain (BTEB1-DBD) bound to GC-rich regions within the TRβ promoter. Using chromatin immunoprecipitation assay, we found that BTEB1 associates with the TRβ promoter in vivo in a T3-dependent manner in both brain and tail. In transfection assays, overexpression of BTEB1 in Xenopus XTC-2 cells accelerated the autoinduction of the TRβ promoter. Finally, overexpression of BTEB1-DBD in XTC-2 cells resulted in dominant negative activity on the TRβ promoter, reducing basal/and T3-induced expression. Our data support the hypothesis that BTEB1 binds to the TRβ promoter in vivo and may play a role in the autoinduction of TRβ during metamorphosis (supported by NSF grant IBN 9724080 to R.J.D.)