Functional identification and evolutionary conservation of the yme1L1 mitochondrial integrity gene promoter

• The yme1L1 promoter is a TATA-less, dispersed transcription start site promoter.
• The functionally-defined yme1L1 proximal promoter sequence is an evolutionarily conserved CpG island.
• Sp1 and Ets/ELK-1 sites are evolutionarily conserved in the yme1L1 promoter.
• Sp1 and Ets/ELK-1 consensus binding sites are required for yme1L1 promoter activity.

Yme1-like 1 (yme1L1) is a mouse ortholog of Saccharomyces cerevisiae yme1p, a protein that degrades unfolded or misfolded mitochondrial gene products and is essential for protecting mitochondrial morphology and mitochondrial genome integrity. Other yme1L1 gene family members are responsible for several human paralytic diseases, suggesting yme1L1 may eventually be linked to a paralytic disease that is currently of unknown etiology. Although the mouse and human YME1L1 promoters show evolutionary conservation of sequences, the mouse yme1L1 promoter does not have target consensus sequences for the MURE1, CHOP, and MURE2 transcription factors as found in the human promoter. Bioinformatics analyses allowed for the identification of the mouse yme1L1 promoter, several conserved and potentially important transcription factor binding sites, the promoter as a CpG island, and confirmation of evolutionary conservation among ten orthologous species promoter regions. Isolation and initial characterization through 5′ RACE and transient transfection has identified the dispersed start sites of transcription for this TATA-less promoter and confirmed proximal and core promoter activity.