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J Proteome Res. 2015 Sep 4;14(9):3635-44. doi: 10.1021/acs.jproteome.5b00565. Epub 2015 Aug 18.

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

Fan Y1,2,3, Zhang Y1,2,3, Xu S2, Kong N1,2,3, Zhou Y1,2,3, Ren Z2, Deng Y1,2,3, Lin L2, Ren Y2, Wang Q1,2,3, Zi J2, Wen B2, Liu S1,2,3.

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CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , No 1, Beichen West Road, Beijing 100101, China.
BGI-Shenzhen , Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
Graduate University of the Chinese Academy of Sciences , 19A, Yuquan Road, Beijing 100049, China.


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.


CHPP; DHS; ENCODE; TF; histone modification; missing proteins; proteome; β-defensin

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