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Systematic Dissection of Coding Exons at Single Nucleotide Resolution Supports an Additional Role in Cell-Specific Transcriptional Regulation
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نویسنده
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birnbaum r.y. ,patwardhan r.p. ,kim m.j. ,findlay g.m. ,martin b. ,zhao j. ,bell r.j.a. ,smith r.p. ,ku a.a. ,shendure j. ,ahituv n.
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منبع
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plos genetics - 2014 - دوره : 10 - شماره : 10
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چکیده
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In addition to their protein coding function,exons can also serve as transcriptional enhancers. mutations in these exonic-enhancers (eexons) could alter both protein function and transcription. however,the functional consequence of eexon mutations is not well known. here,using massively parallel reporter assays,we dissect the enhancer activity of three liver eexons (sorl1 exon 17,traf3ip2 exon 2,pparg exon 6) at single nucleotide resolution in the mouse liver. we find that both synonymous and non-synonymous mutations have similar effects on enhancer activity and many of the deleterious mutation clusters overlap known liver-associated transcription factor binding sites. carrying a similar massively parallel reporter assay in hela cells with these three eexons found differences in their mutation profiles compared to the liver,suggesting that enhancers could have distinct operating profiles in different tissues. our results demonstrate that eexon mutations could lead to multiple phenotypes by disrupting both the protein sequence and enhancer activity and that enhancers can have distinct mutation profiles in different cell types. © 2014 birnbaum et al.
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آدرس
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department of bioengineering and therapeutic sciences,university of california san francisco,san francisco,ca,united states,institute for human genetics,university of california san francisco,san francisco,ca,united states,department of life sciences,ben-gurion university at the negev,beer-sheva, Israel, department of genome sciences,university of washington,seattle,wa, United States, department of bioengineering and therapeutic sciences,university of california san francisco,san francisco,ca,united states,institute for human genetics,university of california san francisco,san francisco,ca, United States, department of genome sciences,university of washington,seattle,wa, United States, department of genome sciences,university of washington,seattle,wa, United States, department of bioengineering and therapeutic sciences,university of california san francisco,san francisco,ca,united states,institute for human genetics,university of california san francisco,san francisco,ca,united states,key laboratory of advanced control and optimization for chemical processes of the ministry of education,east china university of science and technology,shanghai, China, institute for human genetics,university of california san francisco,san francisco,ca,united states,department of neurological surgery,university of california san francisco,san francisco,ca,united states,biomedical sciences (bms) graduate program,university of california san francisco,san francisco,ca, United States, department of bioengineering and therapeutic sciences,university of california san francisco,san francisco,ca,united states,institute for human genetics,university of california san francisco,san francisco,ca, United States, department of bioengineering and therapeutic sciences,university of california san francisco,san francisco,ca,united states,institute for human genetics,university of california san francisco,san francisco,ca, United States, department of genome sciences,university of washington,seattle,wa, United States, department of bioengineering and therapeutic sciences,university of california san francisco,san francisco,ca,united states,institute for human genetics,university of california san francisco,san francisco,ca, United States
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Authors
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