A Combinatorial Code for Gene Expression Generated by Transcription Factor Bach2 and MAZR (MAZ-Related Factor) through the BTB/POZ Domain

Abstract

Bach2 is a B-cell-and neuron-specific transcription repressor that forms heterodimers with theEukaryotic genes are most often regulated by the simultaneous, synergistic activity of several transcription factors. Protein-protein interactions play important roles in synergistic activity among these factors. In this respect, the BTB/POZ domain (2, 4, 43) may be of particular interest because of its recurrent presence in transcription factors and its activity with regard to directing specific interactions. The genome project of Caenorhabditis elegans revealed that worms possess more than 100 genes that code for BTB/POZ domain proteins. Thus the BTB/POZ domain constitutes one of the largest families of protein domains in multicellular organisms (10). Interestingly, transcription factors encoding this domain are thought to play a variety of structural and organizational roles (1,2,4,13,21,34,35). For example, the Drosophila GAGA factor is involved in chromatin remodeling and in mediating enhancer-promoter interactions (34). Alterations of the PLZF and BCL6 genes, both encoding BTB/POZ factors, are associated with oncogenesis (9, 41). BTB/POZ domains appear to direct specific protein-protein interactions. However, the exact significance of such interactions in transcription regulation remains unclear.The mammalian transcription factors Bach1 and Bach2 (36) belong to the CNC-related bZip factors that include the hematopoietic factors NF-E2 p45 (3), Nrf1 (6,7,28), Nrf2 (18,31), and Nrf3 (24). Among these factors, Bach1 and Bach2 are unique in that they each possess a BTB/POZ domain. The CNC-related factors form heterodimers with the Maf-related factors through the leucine zippers and bind to the DNA sequence motif called MARE, which contains an AP-1 binding sequence. MARE is found in regulatory regions of various genes like ␤-globin genes, immunoglobulin heavy-chain genes, antioxidant response genes (e.g., GST genes), and crystallin genes (20). These observations suggest that transcription factors binding to the MARE may play important roles in a variety of vertebrate cell types and that only very few of the actual target genes of the CNC family have been identified.Among the CNC-related factors, Bach1 and Bach2 function as transcription repressors. In B cells, Bach2 represses the immunoglobulin heavy-chain 3Ј enhancer, or LCR, perhaps through binding to the corepressor SMRT (32). Since Bach2 possesses the BTB/POZ domain in the N terminus, it may regulate gene expression by interacting with other factors through the BTB/POZ domain. In this study, we identified a new BTB/POZ domain factor, MAZR, which associates with Bach2 through the BTB/POZ domain. MAZR stimulated transcription despite of its lack of any apparent transcription activation domain. Rather, BTB/POZ-mediated oligomer formation was important for transcriptional activity, suggesting that MAZR might be not a typical transactivator but an architectural transcription factor like Drosophila GAGA factor (21). Together with previous observations, our results suggest...

POZ-, AT-hook-, and Zinc Finger-containing Protein (PATZ) Interacts with Human Oncogene B Cell Lymphoma 6 (BCL6) and Is Required for Its Negative Autoregulation

“…The PATZ1 gene encodes four main alternative proteins ranging from 537 to 687 amino acids that contain an N-terminal POZ domain, one or two AT-hooks in the central region, and four to six C2H2 zinc finger motifs at the C terminus (1)(2)(3). Both the AT-hooks and the POZ domain are characteristic of protein factors involved in gene transcription by interacting with a number of other protein factors.…”

Drosophila BTB/POZ Domains of “ttk Group” Can Form Multimers and Selectively Interact with Each Other

“…Rarely, heterodimerization of two different BTBs has been observed. For example, there is indirect experimental evidence that PLZF and FAZF, 14 Bach2 and MAZR, 15 and Miz1 and Bcl6 16 participate in gene regulation through BTB-BTB interactions.…”

POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) inhibits endothelial cell senescence through a p53 dependent pathway

“…13 Although the physiological role of PATZ1 is not clear, experimental evidence suggests that it is a potential transcription regulator. 11,13,14 PATZ1 can function as a transcriptional repressor of basal transcription or as a corepressor of RNF4 RING finger protein-mediated transcription activation on the c-myc, CDC6, galectin-1 and SV40 promoters. 14 PATZ1 negatively regulates CD8 expression in double-negative thymocytes by binding to the CD8 enhancer and interacting with the nuclear receptor corepressor N-CoR complex.…”

“…15 In contrast, PATZ1 acts as a transcriptional activator of the c-myc promoter in B cells, and transcriptional activation by BACH2 is enhanced by its interaction with the BTB/POZ domain of PATZ1. 13 In carcinogenesis, PATZ1 has been found to fuse to the Ewing sarcoma gene (EWS) by a submicroscopic inversion of 22q, resulting in activation of EWS in soft tissue sarcoma, suggesting that PATZ1 might have a potential tumor suppressor function. 16 PATZ1 could also be a potential proto-oncogene in colorectal cancer, as PATZ1 expression is increased in colorectal cancer tissues, PATZ1 upregulation promotes cell growth and its knockdown inhibits cell proliferation.…”