scholarly journals Functional Interactions of Transcription Factor Human GA-binding Protein Subunits

1998 ◽  
Vol 273 (45) ◽  
pp. 29302-29308 ◽  
Author(s):  
Fumihiko Suzuki ◽  
Masahide Goto ◽  
Chika Sawa ◽  
Seiichiro Ito ◽  
Hajime Watanabe ◽  
...  
2016 ◽  
Vol 33 (5) ◽  
pp. 1231-1244 ◽  
Author(s):  
Alvaro Perdomo-Sabogal ◽  
Katja Nowick ◽  
Ilaria Piccini ◽  
Ralf Sudbrak ◽  
Hans Lehrach ◽  
...  

1998 ◽  
Vol 12 (8) ◽  
pp. 1241-1249 ◽  
Author(s):  
Norihiko Yokomori ◽  
Masato Tawata ◽  
Tukasa Saito ◽  
Hiroki Shimura ◽  
Toshimasa Onaya

Abstract The GA-binding protein (GABP), a transcription factor with a widespread tissue distribution, consists of two subunits,α and β1, and acts as a potent positive regulator of various genes. The effect of GABP on transcription of the TSH receptor (TSHR) gene in rat FRTL-5 thyroid cells has now been investigated. Both deoxyribonuclease I footprint analysis and gel mobility-shift assays indicated that bacterially expressed glutathione S-transferase fusion proteins of GABP subunits bind to a region spanning nucleotides (nt) −116 to −80 of the TSHR gene. In gel mobility-shift assays, nuclear extracts of FRTL-5 cells and FRT cells yielded several specific bands with a probe comprising nt −116 to− 80. Supershift assays with antibodies to GABPα and to GABPβ1 showed that GABP was a component of the probe complexes formed by the nuclear extracts. Immunoblot analysis confirmed the presence of both GABP subunits in the nuclear extracts. A reporter gene construct containing the TSHR gene promoter was activated, in a dose-dependent manner, in FRTL-5 cells by cotransfection with constructs encoding both GABPα and GABPβ1. Both GABP binding to and activation of the TSHR gene promoter were prevented by methylation of CpG sites at nt −93 and− 85. These CpG sites were highly methylated (>82%) in FRT cells and completely demethylated in FRTL-5 cells, consistent with expression of the TSHR gene in the latter, but not the former. These results suggest that GABP regulates transcription of the TSHR gene in a methylation-dependent manner and that methylation of specific CpG sites and the methylation sensitivity of GABP contribute to the failure of FRT cells to express the endogenous TSHR gene.


2007 ◽  
Vol 27 (9) ◽  
pp. 3470-3480 ◽  
Author(s):  
Debra A. O'Leary ◽  
Peter G. Noakes ◽  
Nick A. Lavidis ◽  
Ismail Kola ◽  
Paul J. Hertzog ◽  
...  

ABSTRACT The GA-binding protein (GABP) transcription factor has been shown in vitro to regulate the expression of the neuromuscular proteins utrophin, acetylcholine esterase, and acetylcholine receptor subunits δ and ε through the N-box promoter motif (5′-CCGGAA-3′), but its in vivo function remains unknown. A single point mutation within the N-box of the gene encoding the acetylcholine receptor ε subunit has been identified in several patients suffering from postsynaptic congenital myasthenic syndrome, implicating the GA-binding protein in neuromuscular function and disease. Since conventional gene targeting results in an embryonic-lethal phenotype, we used conditional targeting to investigate the role of GABPα in neuromuscular junction and skeletal muscle development. The diaphragm and soleus muscles from mutant mice display alterations in morphology and distribution of acetylcholine receptor clusters at the neuromuscular junction and neurotransmission properties consistent with reduced receptor function. Furthermore, we confirmed decreased expression of the acetylcholine receptor ε subunit and increased expression of the γ subunit in skeletal muscle tissues. Therefore, the GABP transcription factor aids in the structural formation and function of neuromuscular junctions by regulating the expression of postsynaptic genes.


2012 ◽  
Vol 28 (4) ◽  
pp. 846-855 ◽  
Author(s):  
Mervi Ristola ◽  
Satu Arpiainen ◽  
Toshibumi Shimokawa ◽  
Chisei Ra ◽  
Jukka Tienari ◽  
...  

2019 ◽  
Vol 20 (5) ◽  
pp. 1093 ◽  
Author(s):  
Shunya Goto ◽  
Masashi Takahashi ◽  
Narumi Yasutsune ◽  
Sumiki Inayama ◽  
Dai Kato ◽  
...  

Mitotic bookmarking constitutes a mechanism for transmitting transcriptional patterns through cell division. Bookmarking factors, comprising a subset of transcription factors (TFs), and multiple histone modifications retained in mitotic chromatin facilitate reactivation of transcription in the early G1 phase. However, the specific TFs that act as bookmarking factors remain largely unknown. Previously, we identified the “early G1 genes” and screened TFs that were predicted to bind to the upstream region of these genes, then identified GA-binding protein transcription factor alpha subunit (GABPA) and Sp1 transcription factor (SP1) as candidate bookmarking factors. Here we show that GABPA and multiple histone acetylation marks such as H3K9/14AC, H3K27AC, and H4K5AC are maintained at specific genomic sites in mitosis. During the M/G1 transition, the levels of these histone acetylations at the upstream regions of genes bound by GABPA in mitosis are decreased. Upon depletion of GABPA, levels of histone acetylation, especially H4K5AC, at several gene regions are increased, along with transcriptional induction at 1 h after release. Therefore, we proposed that GABPA cooperates with the states of histone acetylation to act as a novel bookmarking factor which, may negatively regulate transcription during the early G1 phase.


Sign in / Sign up

Export Citation Format

Share Document