title: TCERG1 inhibits C/EBPα through a mechanism that does not involve sequestration of C/EBPα at pericentromeric heterochromatin.
abstract: Transcriptional elongation regulator 1 (TCERG1) is a nuclear protein that participates in multiple events that include regulating the elongation of RNA polymerase II and coordinating transcription and pre-mRNA processing. More recently, we showed that TCERG1 is also a specific inhibitor of the transcription factor CCAAT enhancer binding protein α (C/EBPα). Interestingly, the inhibition of C/EBPα by TCERG1 is associated with the relocalization of TCERG1 from the nuclear speckle compartment to the pericentromeric regions where C/EBPα resides. In the present study, we examined additional aspects of C/EBPα-induced redistribution of TCERG1. Using several mutants of C/EBPα, we showed that C/EBPα does not need to be transcriptionally competent or have anti-proliferative activity to induce TCERG1 relocalization. Moreover, our results show that C/EBPα does not need to be localized to the pericentromeric region in order to relocalize TCERG1. This conclusion was illustrated through the use of a V296A mutant of C/EBPα, which is incapable of binding to the pericentromeric regions of heterochromatin and thus takes on a dispersed appearance in the nucleus. This mutant retained the ability to redistribute TCERG1, however in this case the redistribution was from the nuclear speckle pattern to the dispersed phenotype of C/EBPα V296A. Moreover, we showed that TCERG1 was still able to inhibit the activity of the V296A mutant. While we previously hypothesized that TCERG1 might inhibit C/EBPα by keeping it sequestered at the pericentromeric regions, our new findings indicate that TCERG1 can inhibit C/EBPα activity regardless of the latter's location in the nucleus.
authors.affiliation: Department of Biochemistry, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.
authors.forename: Banafsheh
authors.initials: B
authors.lastname: Moazed
authors.forename: Shanna L
authors.initials: SL
authors.lastname: Banman
authors.forename: Grey A
authors.initials: GA
authors.lastname: Wilkinson
authors.forename: William J
authors.initials: WJ
authors.lastname: Roesler
mesh_terms: D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D019556:COS Cells; D059447:Cell Cycle Checkpoints; D002467:Cell Nucleus / Q000378:metabolism; D002503:Centromere / Q000378:metabolism*; D002522:Chlorocebus aethiops; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006570:Heterochromatin / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D020125:Mutation, Missense; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D035602:Transcriptional Elongation Factors / Q000378:metabolism*
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D006570:Heterochromatin; D011993:Recombinant Fusion Proteins; C108440:TCERG1 protein, human; D035602:Transcriptional Elongation Factors; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins