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DOI10.1126/SCIENCE.AAZ3090
Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates
Wang W.; Hu C.-K.; Zeng A.; Alegre D.; Hu D.; Gotting K.; Granillo A.O.; Wang Y.; Robb S.; Schnittker R.; Zhang S.; Alegre D.; Li H.; Ross E.; Zhang N.; Brunet A.; Alvarado A.S.
发表日期2020
ISSN0036-8075
卷号369期号:6508
英文摘要Vertebrates vary in their ability to regenerate, and the genetic mechanisms underlying such disparity remain elusive. Comparative epigenomic profiling and single-cell sequencing of two related teleost fish uncovered species-specific and evolutionarily conserved genomic responses to regeneration. The conserved response revealed several regeneration-responsive enhancers (RREs), including an element upstream to inhibin beta A (inhba), a known effector of vertebrate regeneration. This element activated expression in regenerating transgenic fish, and its genomic deletion perturbed caudal fin regeneration and abrogated cardiac regeneration altogether. The enhancer is present in mammals, shares functionally essential activator protein 1 (AP-1) - binding motifs, and responds to injury, but it cannot rescue regeneration in fish. This work suggests that changes in AP-1 - enriched RREs are likely a crucial source of loss of regenerative capacities in vertebrates. Copyright © 2020 The Authors, some rights reserved.
英文关键词inhibin A; transcription factor AP 1; histone; inhibin; inhibin beta A subunit; transcription factor AP 1; genomics; shape analysis; teleost; vertebrate; animal cell; animal tissue; Article; binding site; bioinformatics; blastema; controlled study; enhancer region; gene activity; gene deletion; gene expression; heart regeneration; inhba gene; killifish; nonhuman; Nothobranchius furzeri; prediction; priority journal; regeneration responsive enhancer; sexual maturation; species difference; tissue regeneration; zebra fish; animal; chemistry; enhancer region; gene expression profiling; genetic epigenesis; genetics; metabolism; molecular evolution; physiology; protein motif; regeneration; single cell analysis; transcription initiation; Mammalia; Teleostei; Vertebrata; Amino Acid Motifs; Animals; Enhancer Elements, Genetic; Epigenesis, Genetic; Evolution, Molecular; Gene Expression Profiling; Histones; Inhibin-beta Subunits; Killifishes; Regeneration; RNA-Seq; Single-Cell Analysis; Transcription Factor AP-1; Transcriptional Activation; Zebrafish
语种英语
来源期刊Science
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/245957
作者单位Stowers Institute for Medical Research, Kansas City, MO 64110, United States; Howard Hughes Medical Institute, Kansas City, MO 64110, United States; Department of Genetics, Stanford University, Stanford, CA 94305, United States; Glenn Laboratories for the Biology of Aging, Stanford University, Stanford, CA 94305, United States
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Wang W.,Hu C.-K.,Zeng A.,et al. Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates[J],2020,369(6508).
APA Wang W..,Hu C.-K..,Zeng A..,Alegre D..,Hu D..,...&Alvarado A.S..(2020).Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates.Science,369(6508).
MLA Wang W.,et al."Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates".Science 369.6508(2020).
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