TCERG1 inhibits C/EBPα through a mechanism that does not involve sequestration of C/EBPα at pericentromeric heterochromatin

• Published in: Journal of cellular biochemistry Vol. 112; no. 9; pp. 2317 - 2326
• Main Authors: Moazed, Banafsheh, Banman, Shanna L., Wilkinson, Grey A., Roesler, William J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2011
• Subjects: Animals; CCAAT enhancer binding protein; CCAAT-Enhancer-Binding Protein-alpha - genetics; CCAAT-Enhancer-Binding Protein-alpha - metabolism; CCAAT-Enhancer-Binding Protein-beta - metabolism; Cell Cycle Checkpoints; Cell Nucleus - metabolism; Centromere - metabolism; Cercopithecus aethiops; confocal microscopy; COS Cells; Green Fluorescent Proteins - metabolism; Heterochromatin - metabolism; Humans; Microscopy, Fluorescence; Mutation, Missense; nuclear speckles; Protein Transport; Recombinant Fusion Proteins - metabolism; subnuclear compartmentalization; TCERG1; Transcriptional Elongation Factors - metabolism
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.23154

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. J. Cell. Biochem. 112: 2317–2326, 2011. © 2011 Wiley‐Liss, Inc.