Insights from ENCODE on Missing Proteins: Why β-Defensin Expression Is Scarcely Detected.

β-Defensins (DEFBs) have a variety of functions. The majority of these proteins were not identified in a recent proteome survey. Neither protein detection nor the analysis of transcriptomic data based on RNA-seq data for three liver cancer cell lines identified any expression products. Extensive investigation into DEFB transcripts in over 70 cell lines offered similar results. This fact naturally begs the question—Why are DEFB genes scarcely expressed? After examining DEFB gene annotation and the physicochemical properties of its protein products, we postulated that regulatory elements could play a key role in the resultant poor transcription of DEFB genes. Four regions containing DEFB genes and six adjacent regions on chromosomes 6, 8, and 20 were carefully investigated using The Encyclopedia of DNA Elements (ENCODE) information, such as that of DNase I hypersensitive sites (DHSs), transcription factors (TFs), and histone modifications. The results revealed that the intensities of these ENCODE features were globally weaker than those in the adjacent regions. Impressively, DEFB-related regions on chromosomes 6 and 8 containing several non-DEFB genes had lower ENCODE feature intensities, indicating that the absence of DEFB mRNAs might not depend on the gene family but may be reliant upon gene location and chromatin structure.