2023,
Science.
DOI:
10.1126/science.abn7930
Mammalian evolution of human cis-regulatory elements and transcription factor binding sites
Gregory Andrews, Kaili Fan, Henry E. Pratt, Nishigandha Phalke, Elinor K. Karlsson, Kerstin Lindblad-Toh, Steven Gazal, Jill E. Moore, Zhiping Weng, Gregory Andrews, Joel C. Armstrong, Matteo Bianchi, Bruce W. Birren, Kevin R. Bredemeyer, Ana M. Breit, Matthew J. Christmas, Hiram Clawson, Joana Damas, Federica Di Palma, Mark Diekhans, Michael X. Dong, Eduardo Eizirik, Kaili Fan, Cornelia Fanter, Nicole M. Foley, Karin Forsberg-Nilsson, Carlos J. Garcia, John Gatesy, Steven Gazal, Diane P. Genereux, Linda Goodman, Jenna Grimshaw, Michaela K. Halsey, Andrew J. Harris, Glenn Hickey, Michael Hiller, Allyson G. Hindle, Robert M. Hubley, Graham M. Hughes, Jeremy Johnson, David Juan, Irene M. Kaplow, Elinor K. Karlsson, Kathleen C. Keough, Bogdan Kirilenko, Klaus-Peter Koepfli, Jennifer M. Korstian, Amanda Kowalczyk, Sergey V. Kozyrev, Alyssa J. Lawler, Colleen Lawless, Thomas Lehmann, Danielle L. Levesque, Harris A. Lewin, Xue Li, Abigail Lind, Kerstin Lindblad-Toh, Ava Mackay-Smith, Voichita D. Marinescu, Tomas Marques-Bonet, Victor C. Mason, Jennifer R. S. Meadows, Wynn K. Meyer, Jill E. Moore, Lucas R. Moreira, Diana D. Moreno-Santillan, Kathleen M. Morrill, Gerard Muntané, William J. Murphy, Arcadi Navarro, Martin Nweeia, Sylvia Ortmann, Austin Osmanski, Benedict Paten, Nicole S. Paulat, Andreas R. Pfenning, BaDoi N. Phan, Katherine S. Pollard, Henry E. Pratt, David A. Ray, Steven K. Reilly, Jeb R. Rosen, Irina Ruf, Louise Ryan, Oliver A. Ryder, Pardis C. Sabeti, Daniel E. Schäffer, Aitor Serres, Beth Shapiro, Arian F. A. Smit, Mark Springer, Chaitanya Srinivasan, Cynthia Steiner, Jessica M. Storer, Kevin A. M. Sullivan, Patrick F. Sullivan, Elisabeth Sundström, Megan A. Supple, Ross Swofford, Joy-El Talbot, Emma Teeling, Jason Turner-Maier, Alejandro Valenzuela, Franziska Wagner, Ola Wallerman, Chao Wang, Juehan Wang, Zhiping Weng, Aryn P. Wilder, Morgan E. Wirthlin, James R. Xue, Xiaomeng Zhang,
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.
2023-10-30 22:31:00
小年:
#paper Andrews G, Fan K, Pratt HE, Phalke N; Zoonomia Consortium§; Karlsson EK, Lindblad-Toh K, Gazal S, Moore JE, Weng Z. Mammalian evolution of human cis-regulatory elements and transcription factor binding sites. Science. 2023 Apr 28;380(6643):eabn7930. doi: 10.1126/science.abn7930. Epub 2023 Apr 28. PMID: 37104580.
哺乳动物之所以具有高度的生物体复杂性，很大程度上是由于它们的蛋白质调节的多样性。描述人类基因组的调控景观是现代生物学的一个长期目标。现代方法测量全基因组的生化信号，包括染色质可及性、组蛋白修饰、DNA甲基化和人类基因组中约1600个转录因子(tf)的结合。本篇文章作者利用Zoonomia项目（Zoonomia project）开发的工具---胎盘哺乳动物的进化限制（evolutionary constraint）和无参考基因组的241种哺乳动物的基因组比对---对胎盘哺乳动物的进化动态进行了研究。作者探索了从表观基因组学数据中获得的ENCODE cCRE和从染色质免疫沉淀数据中获得的367种转录因子的结合位点。他们发现了哺乳动物调控元件的保护性图谱：一端是高度保守的cCRE和进化受限的TFBS，另一端是灵长类动物特有的与转座因子（transposable element）重叠的cCRE和TFBSs。保守性的调控元件主要位于在基本细胞过程（代谢、发育）中起作用的基因附近，并且在其他哺乳动物的基因组中往往具有功能性，而不存在进化限制的调控元件位于涉及与环境相互作用的基因附近。