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<p>Annotation of regulatory elements is essential for understanding mechanisms underlying gene regulation, particularly tissue-specific regulation in human and animals. Here, we characterize 274,682 enhancers and 25,975 promoters across 24 tissues from an adult female sheep using ChIP-seq, ATAC-seq, CAGE-seq, RRBS, WGBS, and RNA-seq. We identify seven neural development-related genes with over 10 enhancers in brain tissues, highlighting the role of tissue-specific regulation. Cis-regulatory enhancer-promoter combinations provide insights into tissue-specific enhancers, such as the cerebellum-specific enhancer (<i>chr15</i>: <i>57390520-57390685</i>) regulating <i>BDNF</i>, which is expressed in both the cerebellum and cerebral cortex. Comparative analysis of enhancer-promoter combinations in human, mouse, pig, cattle, and sheep reveals ruminant-specific pathways, including pentose catabolism and long-chain fatty acid import regulation. A milk fat yield quantitative trait locus (QTL) identified within an enhancer interacts with the fat metabolism-related gene <i>COMMD1</i>, and a birth weight-associated QTL detected within a cerebellum-specific enhancer regulates <i>XKR4</i>. This study provides a robust framework for exploring cis-regulatory mechanisms and tissue-specific regulation, advancing the functional annotation of the sheep reference genome.</p>

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Identification of cis-regulatory elements provides insights into tissue-specific gene regulation in the sheep genome

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月16日

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  • Shangqian Xie,
  • Kimberly M. Davenport,
  • Mazdak Salavati,
  • Alex Caulton,
  • Emily L. Clark,
  • Alan L. Archibald,
  • Shannon M. Clarke,
  • Rudiger Brauning,
  • Alisha T. Massa,
  • Michelle R. Mousel,
  • Stephen N. White,
  • Kim C. Worley,
  • Gordon K. Murdoch,
  • Gabrielle Becker,
  • Morgan R. Stegmiller,
  • Sarem F. Khilji,
  • Katie A. Shira,
  • Temitayo A. Olagunju,
  • Tracy Hadfield,
  • Stephanie D. McKay,
  • Benjamin D. Rosen,
  • Noelle E. Cockett,
  • Timothy P. L. Smith,
  • Brenda M. Murdoch

摘要

Annotation of regulatory elements is essential for understanding mechanisms underlying gene regulation, particularly tissue-specific regulation in human and animals. Here, we characterize 274,682 enhancers and 25,975 promoters across 24 tissues from an adult female sheep using ChIP-seq, ATAC-seq, CAGE-seq, RRBS, WGBS, and RNA-seq. We identify seven neural development-related genes with over 10 enhancers in brain tissues, highlighting the role of tissue-specific regulation. Cis-regulatory enhancer-promoter combinations provide insights into tissue-specific enhancers, such as the cerebellum-specific enhancer (chr15: 57390520-57390685) regulating BDNF, which is expressed in both the cerebellum and cerebral cortex. Comparative analysis of enhancer-promoter combinations in human, mouse, pig, cattle, and sheep reveals ruminant-specific pathways, including pentose catabolism and long-chain fatty acid import regulation. A milk fat yield quantitative trait locus (QTL) identified within an enhancer interacts with the fat metabolism-related gene COMMD1, and a birth weight-associated QTL detected within a cerebellum-specific enhancer regulates XKR4. This study provides a robust framework for exploring cis-regulatory mechanisms and tissue-specific regulation, advancing the functional annotation of the sheep reference genome.