Mammalian evolution of human cis-regulatory elements and transcription factor binding sites
Citations Over TimeTop 1% of 2023 papers
Abstract
Understanding the regulatory landscape of the human genome is a long-standing objective of modern biology. Using the reference-free alignment across 241 mammalian genomes produced by the Zoonomia Consortium, we charted evolutionary trajectories for 0.92 million human candidate cis-regulatory elements (cCREs) and 15.6 million human transcription factor binding sites (TFBSs). We identified 439,461 cCREs and 2,024,062 TFBSs under evolutionary constraint. Genes near constrained elements perform fundamental cellular processes, whereas genes near primate-specific elements are involved in environmental interaction, including odor perception and immune response. About 20% of TFBSs are transposable element-derived and exhibit intricate patterns of gains and losses during primate evolution whereas sequence variants associated with complex traits are enriched in constrained TFBSs. Our annotations illuminate the regulatory functions of the human genome.
Related Papers
- → Which transposable elements are active in the human genome?(2007)517 cited
- → Why Transcription Factor Binding Sites Are Ten Nucleotides Long(2012)178 cited
- → Binding Site Analysis of c-Myb: Screening of Potential Binding Sites by Using the Mutation Matrix Derived from Systematic Binding Affinity Measurements(1996)37 cited
- → Use of a selection technique to identify the diversity of binding sites for the yeast RAP1 transcription factor(1994)61 cited
- → Definition and prediction of the full range of transcription factor binding sites--the hepatocyte nuclear factor 1 dimeric site(2002)26 cited