Targeting the GA binding protein beta1L isoform does not perturb lymphocyte development and function.
GA binding protein (GABP) is a ubiquitously expressed Ets family transcription factor that consists of two subunits, GABPalpha and GABPbeta. GABPalpha binds to DNA, and GABPbeta heterodimerizes with GABPalpha and possesses the ability to transactivate target genes. Our previous studies using GABPalpha-deficient mice revealed that GABPalpha is required for the development of both T and B cells. Two splice variants of GABPbeta are generated from the Gabpb1 locus and differ in their carboxy-terminal lengths and sequences. The longer isoform (GABPbeta1L) can homodimerize and thus form alpha(2)beta(2) tetramers depending on the gene context, whereas the shorter isoform (GABPbeta1S) cannot. In this study, we generated mice that are deficient in GABPbeta1L but that retain the expression of GABPbeta1S. Surprisingly, GABPbeta1L-/- mice had normal T- and B-cell development, and mature T and B cells showed normal responses to various stimuli. In contrast, targeting both GABPbeta1L and GABPbeta1S resulted in early embryonic lethality. Because of its incapability of forming homodimers, GABPbeta1S has been suspected to have a dominant negative role in regulating GABP target genes. Our findings argue against such a possibility and rather suggest that GABPbeta1S has a critical role in maintaining the transcriptional activity of the GABPalpha/beta complex.
Xue
Hai-Hui
HH
Department of Microbiology, University of Iowa, 51 Newton Road, BSB 3-710, Iowa City, IA 52246, USA. hai-hui-xue@uiowa.edu
Jing
Xuefang
X
Bollenbacher-Reilley
Julie
J
Zhao
Dong-Mei
DM
Haring
Jodie S
JS
Yang
Baoli
B
Liu
Chengyu
C
Bishop
Gail A
GA
Harty
John T
JT
Leonard
Warren J
WJ
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D020964:Embryo Loss; D005091:Exons / Q000235:genetics; D051268:GA-Binding Protein Transcription Factor / Q000378:metabolism*; D018390:Gene Targeting; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000166:cytology*
D051268:GA-Binding Protein Transcription Factor; C495658:Gabpb1 protein, mouse; D020033:Protein Isoforms