Scholarlink

Background <p>The interplay between 3D genomic structure and transposable elements (TE) in regulating cell state-specific gene expression program is largely unknown. Here, we explore the utilization of TE-derived enhancers in naïve and expanded pluripotent states by integrative analysis of genome-wide Hi-C-defined enhancer interactions, H3K27ac HiChIP profiling and CRISPR-guided TE proteomics landscape.</p> Results <p>We find that short interspersed nuclear elements (SINEs) are the more involved TEs in the active chromatin and 3D genome architecture. In particular, mammalian-wide interspersed repeat (MIR), a SINE family member, is highly associated with naïve-specific genomic interactions compared to the expanded state. Primarily, in the naïve pluripotent state, MIR enhancer is co-opted by ESRRB for naïve-specific gene expression program. This ESRRB and MIR enhancer interaction is crucial for the formation of loops that build a network of enhancers and super-enhancers regulating pluripotency genes. We demonstrate that loss of a ESRRB-bound MIR enhancer impairs self-renewal. We also find that MIR is co-bound by structural protein complex, ESRRB-YY1, in the naïve pluripotent state.</p> Conclusions <p>Altogether, our study highlights the topological regulation of ESRRB on MIR in the naïve potency state.</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

Rewiring of SINE-MIR enhancer topology and Esrrb modulation in expanded and naive pluripotency

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月28日

查看全文
  • Nadia Omega Cipta,
  • Yingying Zeng,
  • Ka Wai Wong,
  • Zi Hao Zheng,
  • Yao Yi,
  • Tushar Warrier,
  • Jian Zhou Teo,
  • Jia Hao Jackie Teo,
  • Yee Jiun Kok,
  • Xuezhi Bi,
  • Reshma Taneja,
  • Derrick Sek Tong Ong,
  • Jian Xu,
  • Florent Ginhoux,
  • Hu Li,
  • Yih-Cherng Liou,
  • Yuin-Han Loh

摘要

Background

The interplay between 3D genomic structure and transposable elements (TE) in regulating cell state-specific gene expression program is largely unknown. Here, we explore the utilization of TE-derived enhancers in naïve and expanded pluripotent states by integrative analysis of genome-wide Hi-C-defined enhancer interactions, H3K27ac HiChIP profiling and CRISPR-guided TE proteomics landscape.

Results

We find that short interspersed nuclear elements (SINEs) are the more involved TEs in the active chromatin and 3D genome architecture. In particular, mammalian-wide interspersed repeat (MIR), a SINE family member, is highly associated with naïve-specific genomic interactions compared to the expanded state. Primarily, in the naïve pluripotent state, MIR enhancer is co-opted by ESRRB for naïve-specific gene expression program. This ESRRB and MIR enhancer interaction is crucial for the formation of loops that build a network of enhancers and super-enhancers regulating pluripotency genes. We demonstrate that loss of a ESRRB-bound MIR enhancer impairs self-renewal. We also find that MIR is co-bound by structural protein complex, ESRRB-YY1, in the naïve pluripotent state.

Conclusions

Altogether, our study highlights the topological regulation of ESRRB on MIR in the naïve potency state.