The Glutamine‐Alanine Repeat Domain of TCERG1 is Required for the Inhibition of the Growth Arrest Activity of C/EBPα

TCERG1 was characterized previously as a repressor of the transcription factor C/EBP alpha through a mechanism that involved relocalization of TCERG1 from nuclear speckles to pericentromeric regions. The inhibitory activity as well as the relocalization activity has been demonstrated to lie in the amino terminal half of the protein, which contains several discrete motifs including an imperfect glutamine-alanine (QA) repeat. In the present study, we showed that deletion of this domain completely abrogated the ability of TCERG1 to inhibit the growth arrest activity of C/EBP alpha. Moreover, the QA repeat deletion mutant of TCERG1 lost the ability to be relocalized from nuclear speckles to pericentromeric regions, and caused an increase in the average size of individual speckles. We also showed that deletion of the QA repeat abrogated the complex formation between TCERG1 and C/EBP alpha. Examination of mutants with varying numbers of QA repeats indicated that a minimal number of repeats are required for inhibitory activity as well as relocalization ability. These data contribute to our overall understanding of how TCERG1 can have gene-specific effects in addition to its more general roles in coordinating transcription elongation and splicing. (C) 2015 Wiley Periodicals, Inc.