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J Proteome Res. 2015 Dec 4;14(12):4967-75. doi: 10.1021/acs.jproteome.5b00567. Epub 2015 Oct 21.

Assessing Transcription Regulatory Elements To Evaluate the Expression Status of Missing Protein Genes on Chromosomes 11 and 19.

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

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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 , 11 Build, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
Graduate University of the Chinese Academy of Sciences , 19A, Yuquan Road, Beijing 100049, China.


During an investigation of missing proteins with the RNA-seq data acquired from three liver cancer cell lines, the majority of the missing protein coding genes (MPGs) located at chromosome 11 (chr11) had no corresponding mRNAs, while a high percentage of the MPGs on chr19 were detected at the mRNA level. The phenomenon, which was also observed in more than 40 cell lines, led to an inquiry of causation of the different transcriptional statuses of the MPGs in the two chromosomes. We hypothesized that the special chromatin structure was a key element to regulate MPG transcription. Upon a systematical comparison of the effects of DNase I hypersensitive sites (DHSs), transcription factors (TFs), and histone modifications toward these genes or MPGs with/without mRNA evidence in chr11 and 19, we attributed the poor transcription of the MPGs to the weak capacity of these transcription regulatory elements, regardless of which chromosome the MPGs were located. We further analyzed the gene contents in chr11 and found a number of genes related to sensory functions in the presence of chr11. We postulate that a high number of sensory-related genes, which are located within special chromatin structure, could bring a low detection rate of MPGs in chr11.


Chromosome-Centric Human Proteome Project; ENCODE; missing proteins; regulatory element; transcriptome

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