Small Maf proteins interact with the human transcription factor TCF11/Nrf1/LCR-F1

Abstract

The human TCF11 gene encodes a ubiquitously expressed bZIP transcription factor of the cap n' collar (CNC) domain family. It has a high sequence similarity to the erythroid-specific bZIP factor p45 NF-E2 in the CNC domain, which is involved in DNA binding. LCR-F1, a TCF11 isoform, is a more potent transcriptional activator than p45 NF-E2 in erythroid cells. We show here that the TCF11 protein interacts to form heterodimers with small Maf proteins, previously shown to dimerize with p45 NF-E2, ECH and Fos. Such heterodimerization significantly alters the DNA binding characteristics of TCF11. While TCF11 alone binds in vitro to the tandem NF-E2 site derived from 5' DNase hypersensitive site 2 in the beta-globin locus control region and to the single NF-E2 site in the porphobilinogen deaminase gene promoter, stronger binding is detected in the presence of small Maf proteins. Using antibodies, TCF11 isoforms bound to the single NF-E2 site were detected in K562 erythroid cell nuclear extracts. These findings place TCF11 as a good candidate for the proposed widely expressed factor(s) known to interact with small Maf proteins and bind NF-E2 sites in a sequence-specific manner resembling NF-E2.

Cloning and expression of human B cell-specific transcription factor BACH2 mapped to chromosome 6q15

“…The small Maf proteins form heterodimers with a family of bZip proteins that show remarkable homology to two invertebrate proteins, CNC and skn-1, which regulate embryonic development in Drosophila melanogaster and Caenorhabditis elegans, respectively (Mohler et al, 1991(Mohler et al, , 1995Bowerman et al, 1992). This family of factors, referred to as the CNC family, include p45 NF-E2, Nrf1/LCR-F1/TCF-11, Nrf2, and Nrf3, all of which are similar in the bZip domain and form heterodimers with small Maf proteins (Andrews et al, 1993a,b;Chan et al, 1993a,b;Ney et al, 1993;Caterina et al, 1994;Moi et al, 1994;Igarashi et al, 1994Igarashi et al, , 1995Marini et al, 1997;Johnsen et al, 1996;Toki et al, 1997;Kobayashi et al, 1999). Gene targeting has revealed distinct roles for several CNC family members in mammalian gene regulation.…”

“…In addition to the bZip domain, Bach proteins share a signature motif called the Bric-a-brac, Tramtrack and Broad complex (BTB) domain which is involved in protein ± protein interactions (Albagli et al, 1995). Heterodimers of small Maf proteins and the CNC-related factors bind to the NF-E2 consensus site (TGCTGA G / C TCA T / C ) which is related to MARE (Caterina et al, 1994;Chan et al, 1993a,b;Johnsen et al, 1996;Marini et al, 1997;Moi et al, 1994;Oyake et al, 1996;Toki et al, 1997). Among these CNC family proteins, the Bach proteins take a unique position in that they function as transcription repressors rather than activators in transient transfection assays (Oyake et al, 1996).…”

Impaired megakaryopoiesis and behavioral defects inmafG-null mutant mice

“…Adding to this regulatory complexity, p45 was subsequently identified as only one member of a larger group of proteins that now constitute the mammalian cap'n'collar (CNC; Mohler et al 1991) protein family-these are called p45, Nrf1 (/LCRF1/TCF11), Nrf2 (/ECH), Bach1, and Bach2 (Chan et al 1993;Caterina et al 1994;Luna et al 1994;Moi et al 1994;Itoh et al 1995;Oyake et al 1996). These five CNC family members display similar heterodimeric interactions, but also include unique differences in transactivation potential in association with the small Maf proteins Johnsen et al 1996;Oyake et al 1996). As noted originally, the MARE also encompasses a consensus AP-1 binding site (Engel 1994).…”

TCF11 at the crossroads of oxidative stress and the ubiquitin proteasome system

“…1). 42,66,67 intra-membrane cleavage, releasing the transcriptional active cytoplasmic part. However, Zhang and colleagues found no evidence for S1P and S2P cleavage of TCF11.…”