GA-binding protein transcription factor: a review of GABP as an integrator of intracellular signaling and protein–protein interactions

Rosmarin, Alan G.; Resendes, Karen K.; Yang, Zhaohui; McMillan, John N.; Fleming, Shawna L.

doi:10.1016/j.bcmd.2003.09.005

Cited by 176 publications

(205 citation statements)

References 96 publications

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“…S10). SP1, YY1, and GABPA have been previously described as interacting partners (Galvagni et al 2001;Rosmarin et al 2004), and these pathway enrichments are consistent with previous studies implicating GABPA in controlling stem cell maintenance and differentiation (Yu et al 2016). …”

Section: Dap Binding Recapitulates Known Liver Expression Programssupporting

confidence: 90%

A genome-wide interactome of DNA-associated proteins in the human liver

et al. 2017

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Large-scale efforts like the ENCODE Project have made tremendous progress in cataloging the genomic binding patterns of DNA-associated proteins (DAPs), such as transcription factors (TFs). However, most chromatin immunoprecipitation-sequencing (ChIP-seq) analyses have focused on a few immortalized cell lines whose activities and physiology differ in important ways from endogenous cells and tissues. Consequently, binding data from primary human tissue are essential to improving our understanding of in vivo gene regulation. Here, we identify and analyze more than 440,000 binding sites using ChIP-seq data for 20 DAPs in two human liver tissue samples. We integrated binding data with transcriptome and phased WGS data to investigate allelic DAP interactions and the impact of heterozygous sequence variation on the expression of neighboring genes. Our tissue-based data set exhibits binding patterns more consistent with liver biology than cell lines, and we describe uses of these data to better prioritize impactful noncoding variation. Collectively, our rich data set offers novel insights into genome function in human liver tissue and provides a valuable resource for assessing disease-related disruptions.

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Section: Dap Binding Recapitulates Known Liver Expression Programssupporting

confidence: 90%

A genome-wide interactome of DNA-associated proteins in the human liver

et al. 2017

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“…GABP is a heterodimeric transcription factor consisting of a DNA-binding ␣ subunit that is a member of the Ets family of transcription factors, and a ␤ subunit containing an ankyrin domain that contains the activation domain (35). We therefore hypothesized that GABP might also interact with the Ets site in developing B cells.…”

Section: An Intact Ets Site Is Essential For Activity Of the Il7r Promentioning

confidence: 99%

Regulation of the Interleukin-7 Receptor α Promoter by the Ets Transcription Factors PU.1 and GA-binding Protein in Developing B Cells

DeKoter

Schweitzer

Kamath

et al. 2007

Journal of Biological Chemistry

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Signaling through the IL-7 receptor (IL-7R) is required for development and maintenance of the immune system. The receptor for IL-7 is heterodimeric, consisting of a common ␥ chain (␥c, encoded by Il2rg) and an ␣ subunit (IL-7R␣, encoded by Il7r). The Il7r gene is expressed specifically in the immune system in a developmental stage-specific manner. It is not known how the Il7r gene is transcriptionally regulated during B cell development. The goal of this study is to elucidate the function of the Il7r promoter region in developing B cells. Using a combination of 5 rapid amplification of cDNA ends analysis, transient transfection assays, and DNase I hypersensitivity mapping, we identified the location of the Il7r promoter. Using a combination of electrophoretic mobility shift analysis, chromatin immunoprecipitation experiments, and RNA interference experiments, we found that the Ets transcription factors PU.1 and GA-binding protein (GABP) activate the Il7r promoter by interacting with a highly conserved Ets binding site. In committed B lineage cells, GABP can promote Il7r transcription in the absence of PU.1. However, the results of retroviral gene transfer experiments suggest that PU.1 is uniquely required to initiate transcription of the Il7r locus at the earliest stages of progenitor B cell generation. In summary, these results suggest that Il7r transcription is regulated by both PU.1 and GABP in developing B cells. The cytokine interleukin-7 (IL-7)2 is essential for development and maintenance of the immune system (reviewed in Ref. 1). IL-7 is produced constitutively by stromal cells of the bone marrow, fetal liver, thymus, and by epithelial cells (2). IL-7 promotes both proliferation and differentiation of developing B and T lymphocytes (3, 4). The receptor for IL-7 (IL-7R, encoded by Il7r) is heterodimeric, consisting of an IL-7-specific ␣ chain (IL-7R␣) and a common ␥ chain (␥c, encoded by Il2rg), which is shared with other subunits comprising the receptors for IL-2, IL-4, IL-9, IL-15, and IL-21. The Il2rg gene is expressed by all hematopoietic cells (5). Transcription of the Il7r gene is initiated in common lymphoid progenitor cells (6). IL-7R␣ is expressed in developing B cells but is down-regulated upon B cell maturation (7,8). In developing T cells, IL-7R␣ is initially down-regulated at the CD4 and CD8 double negative 3 stage of thymic development (9). However, Il7r transcription is re-activated after the CD4 and CD8 double-positive stage and is expressed on peripheral CD4 or CD8 single-positive T cells (7). Therefore, the Il7r gene is expressed in a cell type and developmental stage-specific manner (7, 10). Targeted null mutation of either the Il7r (11, 12) or the Il2rg gene (13, 14) results in a profound block to early B and T cell development in mice. In human patients, mutations in the IL7RA gene cause a type of severe combined immunodeficiency in which the major deficiencies are in T cell development, whereas B and NK cells are relatively normal in number (15). Therefore, the IL-7R␣ is critically ...

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“…Human GABP exists as a heterodimer consisting of an ets helix-loop-helix DNA-binding domain (DBD) subunit (GABPa) and a Notch-ankyrin repeat subunit (GABPb) which contains the activation domain as well as a domain required for the formation of tetrameric complexes (12). GABP has been implicated in the regulation of genes in response to cell growth, activation of respiration-related genes (13), as a downstream mediator of ErbB3 and ErbB4 signaling (14), and recently in connecting mitochondrial metabolism and breast differentiation (15). The interaction of the a-and b-subunits with each other and with other transcription factors defines the ability of GABP to regulate the expression of its target genes.…”

Section: Introductionmentioning

confidence: 99%

The Unliganded Glucocorticoid Receptor Positively Regulates the Tumor Suppressor GeneBRCA1through GABP Beta

Ritter

Antonova

Mueller

2012

Molecular Cancer Research

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Loss of BRCA1 tumor suppressor function is a critical event in breast tumorigenesis. We have previously identified the stress hormone hydrocortisone as a negative regulator of BRCA1 expression in nonmalignant mammary cells. Here, we have identified a direct role for the unliganded glucocorticoid receptor (GR) in BRCA1 upregulation in the absence of hydrocortisone. The positive regulatory effect of GR is lost upon the addition of hydrocortisone. We have shown that GR interacts with the BRCA1 promoter only in the absence of hydrocortisone, and that this interaction is mediated through the b-subunit of the ets transcription factor GA-binding protein (GABP) at the RIBS promoter element. GR and GABPb interact in both coimmunoprecipitation and mammalian two-hybrid assays, and this interaction involves the N-terminal to central regions of both proteins. This work presents the first evidence of a ligand-independent role for GR as a positive regulator of gene expression, and loss of GR from the BRCA1 promoter in response to stress hormones leads to decreased BRCA1 expression. Because low levels of BRCA1 have been implicated in the development of sporadic breast cancer, this may represent a novel mechanism through which prolonged stress signaling increases breast cancer risk. Mol Cancer Res; 10(4); 558-69. Ó2012 AACR. IntroductionGerm line mutations in the BRCA1 tumor suppressor contribute to familial breast tumor formation but BRCA1 mutations do not seem to occur in sporadic breast cancer tumors (1). Instead, sporadic breast tumors exhibit decreased levels of BRCA1 expression, and the degree of downregulation seems to be correlated with tumor grade, rate of tumor progression, and risk of metastasis (2-6). This implies that loss of BRCA1 function, either through decreased activity or downregulation of expression, is a critical event in the etiology of breast cancer. Phenotypically normal breast epithelial cells from individuals harboring a BRCA1 germ line mutation (a so called "one-hit" mutation accompanied by a 50% decrease in BRCA1 function) express an altered mRNA profile compared with normal cells from individuals without a BRCA1 mutation (7). This suggests that decreases in functional BRCA1

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GA-binding protein transcription factor: a review of GABP as an integrator of intracellular signaling and protein–protein interactions

Cited by 176 publications

References 96 publications

A genome-wide interactome of DNA-associated proteins in the human liver

A genome-wide interactome of DNA-associated proteins in the human liver

Regulation of the Interleukin-7 Receptor α Promoter by the Ets Transcription Factors PU.1 and GA-binding Protein in Developing B Cells

The Unliganded Glucocorticoid Receptor Positively Regulates the Tumor Suppressor GeneBRCA1through GABP Beta

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