Systematic target function annotation of human transcription factors

BMC Biology
Yong Fuga Li, Russ B Altman

Abstract

Transcription factors (TFs), the key players in transcriptional regulation, have attracted great experimental attention, yet the functions of most human TFs remain poorly understood. Recent capabilities in genome-wide protein binding profiling have stimulated systematic studies of the hierarchical organization of human gene regulatory network and DNA-binding specificity of TFs, shedding light on combinatorial gene regulation. We show here that these data also enable a systematic annotation of the biological functions and functional diversity of TFs. We compiled a human gene regulatory network for 384 TFs covering the 146,096 TF-target gene (TF-TG) relationships, extracted from over 850 ChIP-seq experiments as well as the literature. By integrating this network of TF-TF and TF-TG relationships with 3715 functional concepts from six sources of gene function annotations, we obtained over 9000 confident functional annotations for 279 TFs. We observe extensive connectivity between TFs and Mendelian diseases, GWAS phenotypes, and pharmacogenetic pathways. Further, we show that TFs link apparently unrelated functions, even when the two functions do not share common genes. Finally, we analyze the pleiotropic functions of TFs and sugges...Continue Reading

References

Apr 5, 2019·Scientific Reports·Lin Yuan, De-Shuang Huang

Citations

Jul 5, 1991·Science·M HollsteinC C Harris
Jan 1, 1989·European Journal of Clinical Pharmacology·H WietholtzS Matern
Jun 5, 1987·Science·T ManiatisJ A Fischer
Feb 14, 1998·Nature Genetics·V PingaultM Goossens
Mar 14, 1998·Journal of Biochemistry·K Sogawa, Y Fujii-Kuriyama
Mar 20, 1999·The Journal of Clinical Endocrinology and Metabolism·R A HegeleB Zinman
Oct 16, 1999·Science·A L Barabasi, R Albert
Nov 5, 1999·The Journal of Clinical Investigation·W M MacfarlaneA T Hattersley
Dec 11, 1999·Nucleic Acids Research·M Kanehisa, S Goto
Mar 13, 2001·Annual Review of Immunology·W Reith, B Mach
Jul 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·H YamashitaK Uyeda
Dec 26, 2001·Nucleic Acids Research·Micheal HewettTeri E Klein
Jan 19, 2002·Genes & Development·Bing RenBrian David Dynlacht
Jul 9, 2002·Molecular and Cellular Biology·Jeffrey D Hildebrand, Philippe Soriano
Oct 25, 2002·Nature·Sato HonmaKen-ichi Honma
Jan 10, 2003·Nucleic Acids Research·D KarolchikUniversity of California Santa Cruz
Jan 10, 2003·Nucleic Acids Research·Gary D BaderChristopher W V Hogue
Mar 12, 2003·Neurology·Alberto AscherioF E Speizer
Mar 13, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ashok Kumar, Aladin M Boriek
Jul 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·John D Storey, Robert Tibshirani
Mar 3, 2004·Nature Genetics·Päivi PajukantaLeena Peltonen
Mar 3, 2004·Nature Reviews. Cancer·P Andrew FutrealMichael R Stratton
Dec 21, 2004·Nucleic Acids Research·G Joshi-TopeL Stein

Related Concepts

Genome-Wide Association Study
Drug Response
Study
Biochemical Pathway
Transcriptional Regulation
Protein Binding
Genome
Genes
Transcription, Genetic
Candidate Disease Gene

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