Mutation of a lysine residue in a homeodomain generates dominant negative thyroid transcription factor 1

Li Yang, Dong Yan, Molly Bruggeman, Hong Du, Cong Yan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Thyroid transcription factor 1 (TTF-1) is a 42 kDa homeodomain (HD) containing the tissue-specific transcription factor of Nkx2 family members (also termed TEBP and Nkx2.1). TTF-1 is an essential transcription factor required for lung development and lung-specific gene expression. Transgenic mice carrying TTF-1 DNA-binding site mutations completely abolish expression of the human surfactant protein B (hSP-B) 1.5 kb lacZ reporter gene in the lung in vivo. Acetylation of transcription factors by nuclear receptor coactivators is an important mechanism for gene regulation. TTF-1 is acetylated by nuclear receptor coactivators including the activator of the thyroid and retinoic acid receptor, CREB-binding protein, and steroid receptor coactivator 1 (SRC-1) in cell transfection and immunoprecipitation studies. A glutathionine transferase pull-down assay shows TTF-1 direct interaction with the SRC-1 histone acetyltransferase domain. Site-specific mutagenesis identifies that the lysine residue at position 182 in the TTF-1 HD is acetylated in respiratory epithelial cells. Mutation at this acetylation site shows a dominant negative effect on SP-B gene transcription. The study supports a concept that acetylation is an important mechanism for TTF-1 activity.

Original languageEnglish (US)
Pages (from-to)12489-12497
Number of pages9
JournalBiochemistry
Volume43
Issue number39
DOIs
StatePublished - Oct 5 2004
Externally publishedYes

Fingerprint

Lysine
Mutation
Acetylation
Nuclear Receptor Coactivators
Nuclear Receptor Coactivator 1
Transcription Factors
Gene expression
Lung
Genes
CREB-Binding Protein
Histone Acetyltransferases
Mutagenesis
Retinoic Acid Receptors
Lac Operon
Transcription
Transferases
Site-Directed Mutagenesis
thyroid nuclear factor 1
Reporter Genes
Immunoprecipitation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Mutation of a lysine residue in a homeodomain generates dominant negative thyroid transcription factor 1. / Yang, Li; Yan, Dong; Bruggeman, Molly; Du, Hong; Yan, Cong.

In: Biochemistry, Vol. 43, No. 39, 05.10.2004, p. 12489-12497.

Research output: Contribution to journalArticle

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