Scholarlink

Background <p>Embryonic development requires the accurate spatiotemporal execution of cell lineage-specific gene expression programs, which are controlled by transcriptional enhancers. Developmental enhancers adopt a primed chromatin state prior to their activation. How this primed enhancer state is established and maintained and how it affects the regulation of developmental gene networks remains poorly understood.</p> Results <p>Here, we use comparative multi-omic analyses of human and mouse early embryonic development to identify subsets of postgastrulation lineage-specific enhancers which are epigenetically primed ahead of their activation, marked by the histone modification H3K4me1 within the epiblast. We show that epigenetic priming occurs at lineage-specific enhancers for all three germ layers and that epigenetic priming of enhancers confers lineage-specific regulation of key developmental gene networks. Surprisingly in some cases, lineage-specific enhancers are epigenetically marked already in the zygote, weeks before their activation during lineage specification. Moreover, we outline a generalizable strategy to use naturally occurring human genetic variation to delineate important sequence determinants of primed enhancer function.</p> Conclusions <p>Our findings identify an evolutionarily conserved program of enhancer priming and begin to dissect the temporal dynamics and mechanisms of its establishment and maintenance during early mammalian development.</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

Epigenetic priming of mammalian embryonic enhancer elements coordinates developmental gene networks

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月18日

查看全文
  • Christopher D. Todd,
  • Jannat Ijaz,
  • Fereshteh Torabi,
  • Oleksandr Dovgusha,
  • Stephen Bevan,
  • Olivia Cracknell,
  • Tim Lohoff,
  • Stephen Clark,
  • Ricard Argelaguet,
  • Juliette Pierce,
  • Ioannis Kafetzopoulos,
  • Alice Santambrogio,
  • Jennifer Nichols,
  • Ferdinand von Meyenn,
  • Ufuk Günesdogan,
  • Stefan Schoenfelder,
  • Wolf Reik

摘要

Background

Embryonic development requires the accurate spatiotemporal execution of cell lineage-specific gene expression programs, which are controlled by transcriptional enhancers. Developmental enhancers adopt a primed chromatin state prior to their activation. How this primed enhancer state is established and maintained and how it affects the regulation of developmental gene networks remains poorly understood.

Results

Here, we use comparative multi-omic analyses of human and mouse early embryonic development to identify subsets of postgastrulation lineage-specific enhancers which are epigenetically primed ahead of their activation, marked by the histone modification H3K4me1 within the epiblast. We show that epigenetic priming occurs at lineage-specific enhancers for all three germ layers and that epigenetic priming of enhancers confers lineage-specific regulation of key developmental gene networks. Surprisingly in some cases, lineage-specific enhancers are epigenetically marked already in the zygote, weeks before their activation during lineage specification. Moreover, we outline a generalizable strategy to use naturally occurring human genetic variation to delineate important sequence determinants of primed enhancer function.

Conclusions

Our findings identify an evolutionarily conserved program of enhancer priming and begin to dissect the temporal dynamics and mechanisms of its establishment and maintenance during early mammalian development.