A short ORF-encoded transcriptional regulator
| Autor: | Michael J. Bollong, James J. Moresco, Minseob Koh, Yeonjin Ko, Peter G. Schultz, Thomas F. Martinez, Insha Ahmad, Michael A. Erb, Alan Saghatelian, Jolene K. Diedrich, Yuxiang Zhang, Qian Chu |
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| Rok vydání: | 2021 |
| Předmět: |
Pan troglodytes
Transcription Genetic Ultraviolet Rays Transgene Computational biology Biology Genome Histones 03 medical and health sciences Mice Open Reading Frames Protein Interaction Mapping Transcriptional regulation Animals Humans Amino Acid Sequence Transgenes Transcription factor Expanded genetic code 030304 developmental biology chemistry.chemical_classification 0303 health sciences Multidisciplinary Sequence Homology Amino Acid Lysine 030302 biochemistry & molecular biology Histone binding protein Biological Sciences Chromatin Amino acid Rats Open reading frame HEK293 Cells chemistry Diazomethane Gene Expression Regulation Genetic Loci Cattle K562 Cells Peptides Sequence Alignment HeLa Cells Protein Binding |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 |
| Popis: | Recent technological advances have expanded the annotated protein coding content of mammalian genomes, as hundreds of previously unidentified, short open reading frame (ORF)-encoded peptides (SEPs) have now been found to be translated. Although several studies have identified important physiological roles for this emerging protein class, a general method to define their interactomes is lacking. Here, we demonstrate that genetic incorporation of the photo-crosslinking noncanonical amino acid AbK into SEP transgenes allows for the facile identification of SEP cellular interaction partners using affinity-based methods. From a survey of seven SEPs, we report the discovery of short ORF-encoded histone binding protein (SEHBP), a conserved microprotein that interacts with chromatin-associated proteins, localizes to discrete genomic loci, and induces a robust transcriptional program when overexpressed in human cells. This work affords a straightforward method to help define the physiological roles of SEPs and demonstrates its utility by identifying SEHBP as a short ORF-encoded transcription factor. |
| Databáze: | OpenAIRE |
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