Activation of the Smooth Muscle-specific Telokin Gene by Thyrotroph Embryonic Factor (TEF)

Jiliang Zhou, April M. Hoggatt, B. Herring

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Transcription of the telokin gene is restricted to smooth muscle cells throughout development, making this gene an excellent model for unraveling the mechanisms that regulate gene expression in smooth muscle tissues. To identify proteins that bind to the telokin promoter, the AT-rich/CArG core of the promoter was used as a probe to perform a Southwestern screen of a mouse bladder cDNA library. Four clones corresponding to two distinct isoforms of mouse thyrotroph embryonic factor (TEFα and TEFβ) were identified from this screen. The two TEF isoforms differ from each other at their amino termini and result from alternative promoter usage. An RNase protection assay showed that both TEF isoforms are expressed at high levels in mouse lung, bladder, kidney, gut, and brain. Gel mobility shift assays demonstrated that purified TEF protein can specifically bind to an AT-rich region within the core of the telokin promoter. Furthermore, when overexpressed in 10T1/2 cells, TEF significantly increased the activity of a telokin promoter-reporter gene; this activation was further augmented by elevated intracellular calcium levels. In contrast, overexpression of TEF had no effect on reporter genes driven by SM22α, smooth muscle α-actin, or smooth muscle myosin heavy chain promoters. Consistent with these results, overexpression of TEFα and TEFβ in A10 cells, using adenoviral vectors, increased expression of endogenous telokin without altering expression of myosin light chain 20, SM22α, smooth muscle α-actin, or calponin. These findings suggest that TEF factors contribute to the activation of the telokin promoter in smooth muscle cells in a calcium-dependent manner. These data also suggest that distinct transcription factors are required to control the expression of different smooth muscle genes in a single tissue.

Original languageEnglish
Pages (from-to)15929-15937
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number16
DOIs
StatePublished - Apr 16 2004

Fingerprint

Thyrotrophs
Smooth Muscle
Muscle
Genes
Chemical activation
Protein Isoforms
Actins
Assays
Cells
AT Rich Sequence
Tissue
Smooth Muscle Myosins
Calcium
Myosin Light Chains
Reporter Genes
Myosin Heavy Chains
Smooth Muscle Myocytes
Transcription
Ribonucleases
Gene Library

ASJC Scopus subject areas

  • Biochemistry

Cite this

Activation of the Smooth Muscle-specific Telokin Gene by Thyrotroph Embryonic Factor (TEF). / Zhou, Jiliang; Hoggatt, April M.; Herring, B.

In: Journal of Biological Chemistry, Vol. 279, No. 16, 16.04.2004, p. 15929-15937.

Research output: Contribution to journalArticle

Zhou, Jiliang ; Hoggatt, April M. ; Herring, B. / Activation of the Smooth Muscle-specific Telokin Gene by Thyrotroph Embryonic Factor (TEF). In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 16. pp. 15929-15937.
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