Scholarlink

<p>Wide variation of responses to identical stimuli presented to genetically inbred mice suggests the hypothesis that stochastic non-genetic variation, such as in chromatin state or enhancer activity during neurodevelopment, can mediate such phenotypic differences. However, this hypothesis is largely untested since capturing pre-existing molecular states requires non-destructive, longitudinal recording. Therefore, we tested the potential of Calling Cards (CC) to record transient neuronal enhancer activity during postnatal development in mice, and thereby associate such non-genetic variation with a subsequent phenotypic presentation – degree of seizure response to the pro-convulsant pentylenetetrazol. We show that recorded differences in enhancer activity at 243 loci predict a severe vs. mild response, and that these are enriched near genes associated with human epilepsy. We also validated pharmacologically a seizure-modifying role for two previously unassociated genes, <i>Htr1f</i> and <i>Let7c</i>. This proof-of-principle supports using CC broadly to discover predisposition loci for other neuropsychiatric traits and behaviors. Finally, as human disease is also influenced by non-genetic factors, similar epigenetic predispositions are possible in humans.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Antecedent enhancer activity predicts future susceptibility to seizures in mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月8日

查看全文
  • Benjamin D. Boros,
  • Mariam A. Gachechiladze,
  • Juanru Guo,
  • Dylan A. Galloway,
  • Shayna M. Mueller,
  • Mark Shabsovich,
  • Allen Yen,
  • Xuhua Chen,
  • Alexander J. Cammack,
  • Tao Shen,
  • Robi D. Mitra,
  • Joseph D. Dougherty,
  • Timothy M. Miller

摘要

Wide variation of responses to identical stimuli presented to genetically inbred mice suggests the hypothesis that stochastic non-genetic variation, such as in chromatin state or enhancer activity during neurodevelopment, can mediate such phenotypic differences. However, this hypothesis is largely untested since capturing pre-existing molecular states requires non-destructive, longitudinal recording. Therefore, we tested the potential of Calling Cards (CC) to record transient neuronal enhancer activity during postnatal development in mice, and thereby associate such non-genetic variation with a subsequent phenotypic presentation – degree of seizure response to the pro-convulsant pentylenetetrazol. We show that recorded differences in enhancer activity at 243 loci predict a severe vs. mild response, and that these are enriched near genes associated with human epilepsy. We also validated pharmacologically a seizure-modifying role for two previously unassociated genes, Htr1f and Let7c. This proof-of-principle supports using CC broadly to discover predisposition loci for other neuropsychiatric traits and behaviors. Finally, as human disease is also influenced by non-genetic factors, similar epigenetic predispositions are possible in humans.