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 language | English (US) |
|---|---|
| Pages (from-to) | 12489-12497 |
| Number of pages | 9 |
| Journal | Biochemistry |
| Volume | 43 |
| Issue number | 39 |
| DOIs | |
| State | Published - Oct 5 2004 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Mutation of a lysine residue in a homeodomain generates dominant negative thyroid transcription factor 1
AU - Yang, Li
AU - Yan, Dong
AU - Bruggeman, Molly
AU - Du, Hong
AU - Yan, Cong
PY - 2004/10/5
Y1 - 2004/10/5
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=4744347908&partnerID=8YFLogxK
U2 - 10.1021/bi049283o
DO - 10.1021/bi049283o
M3 - Article
C2 - 15449938
AN - SCOPUS:4744347908
VL - 43
SP - 12489
EP - 12497
JO - Biochemistry
JF - Biochemistry
SN - 0006-2960
IS - 39
ER -