PMID- 15449938
OWN - NLM
STAT- MEDLINE
DCOM- 20041115
LR  - 20171116
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 43
IP  - 39
DP  - 2004 Oct 5
TI  - Mutation of a lysine residue in a homeodomain generates dominant negative thyroid 
      transcription factor 1.
PG  - 12489-97
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.
FAU - Yang, Li
AU  - Yang L
AD  - Division of Pulmonary Biology, Children's Hospital Medical Center and Department 
      of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, Ohio 
      45229-3039, USA.
FAU - Yan, Dong
AU  - Yan D
FAU - Bruggeman, Molly
AU  - Bruggeman M
FAU - Du, Hong
AU  - Du H
FAU - Yan, Cong
AU  - Yan C
LA  - eng
GR  - R01 HL061803/HL/NHLBI NIH HHS/United States
GR  - R01 HL067862/HL/NHLBI NIH HHS/United States
GR  - HL-061803/HL/NHLBI NIH HHS/United States
GR  - HL-067862/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (NKX2-1 protein, human)
RN  - 0 (Nkx2-1 protein, mouse)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Pulmonary Surfactant-Associated Protein B)
RN  - 0 (Thyroid Nuclear Factor 1)
RN  - 0 (Transcription Factors)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.3.1.- (Acetyltransferases)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (NCOA1 protein, human)
RN  - EC 2.3.1.48 (Ncoa1 protein, mouse)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Acetylation
MH  - Acetyltransferases/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites/genetics
MH  - Cell Line, Tumor
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Enhancer Elements, Genetic/genetics
MH  - Gene Expression Regulation/genetics
MH  - Gene Silencing
MH  - Genes, Reporter
MH  - Histone Acetyltransferases
MH  - Homeodomain Proteins/*genetics/*metabolism
MH  - Humans
MH  - Lac Operon
MH  - Luciferases/antagonists & inhibitors/genetics/metabolism
MH  - Lysine/*genetics/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/antagonists & inhibitors/*genetics/*metabolism
MH  - Nuclear Receptor Coactivator 1
MH  - *Point Mutation
MH  - Pulmonary Alveoli/cytology/metabolism
MH  - Pulmonary Surfactant-Associated Protein B/antagonists & 
      inhibitors/biosynthesis/genetics
MH  - Respiratory Mucosa/cytology/metabolism
MH  - Sequence Deletion
MH  - Thyroid Nuclear Factor 1
MH  - Transcription Factors/antagonists & inhibitors/*genetics/*metabolism
EDAT- 2004/09/29 05:00
MHDA- 2004/11/16 09:00
CRDT- 2004/09/29 05:00
PHST- 2004/09/29 05:00 [pubmed]
PHST- 2004/11/16 09:00 [medline]
PHST- 2004/09/29 05:00 [entrez]
AID - 10.1021/bi049283o [doi]
PST - ppublish
SO  - Biochemistry. 2004 Oct 5;43(39):12489-97. doi: 10.1021/bi049283o.