Paired related homeobox protein-like 1 (Prrxl1) controls its own expression by a transcriptional autorepression mechanism

• Published in: FEBS letters 2014-09, Vol.588 (18), p.3475-3482
• Main Authors: Monteiro, César B., Costa, Mariana F., Reguenga, Carlos, Lima, Deolinda, Castro, Diogo S., Monteiro, Filipe A.
• Format: Article
• Language: English
• Subjects: Animals; Autorepression; Cell Line, Tumor; ChIP; Chromatin immunoprecipitation; Dorsal root ganglia; Dorsal spinal cord; DRG; Feedback, Physiological; Female; Ganglia, Spinal - cytology; Gene Silencing; homeodomain; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Mice; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurons - metabolism; NLS; nuclear localization signal; OAR; Otp-Aristaless-Rax domain; Paired related homeobox protein-like 1; Promoter Regions, Genetic; Protein Binding; Protein Isoforms - genetics; Protein Isoforms - metabolism; Prrxl1; spinal cord; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2014.08.006

•Two evolutionary conserved regions were identified, which mediate binding of Prrxl1 to its own locus.•Prrxl1 recruitment differs between embryonic dorsal root ganglia and spinal cord.•Prrxl1-bound regions mediate transcriptional repression by Prrxl1.•Expression studies confirm that Prrxl1 down-regulates its own expression.•An auto-inhibitory mechanism regulating Prrxl1 transcription is proposed. The homeodomain factor paired related homeobox protein-like 1 (Prrxl1) is crucial for proper assembly of dorsal root ganglia (DRG)–dorsal spinal cord (SC) pain-sensing circuit. By performing chromatin immunoprecipitation with either embryonic DRG or dorsal SC, we identified two evolutionarily conserved regions (i.e. proximal promoter and intron 4) of Prrxl1 locus that show tissue-specific binding of Prrxl1. Transcriptional assays confirm the identified regions can mediate repression by Prrxl1, while gain-of-function studies in Prrxl1 expressing ND7/23 cells indicate Prrxl1 can down-regulate its own expression. Altogether, our results suggest that Prrxl1 uses distinct regulatory regions to repress its own expression in DRG and dorsal SC.