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<p>Identity-specific chromosome conformation must be re-established at each cell division. To uncover how interphase folding is inherited, we developed an approach that segregates chromosome-intrinsic mechanisms from those propagated through the cytoplasm during G1 nuclear reassembly. Inducible degradation of proteins essential for the establishment of nucleocytoplasmic transport during mitotic exit enabled analysis of folding programmes with distinct modes of inheritance. Here we show that genome compartmentalization is driven entirely by chromosome-intrinsic factors. In addition to conventional compartmental segregation, the chromosome-intrinsic folding programme leads to prominent genome-scale microcompartmentalization of mitotically bookmarked <i>cis</i>-regulatory elements. The microcompartment conformation forms transiently during telophase and is subsequently modulated by a second folding programme inherited through the cytoplasm in early G1. This programme includes cohesin-mediated loop extrusion and factors involved in transcription and RNA processing. The combined and interdependent action of chromosome-intrinsic and cytoplasmic inherited folding programmes determines the interphase chromatin conformation as cells exit mitosis.</p>

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Interphase chromosome conformation is specified by distinct folding programmes inherited through mitotic chromosomes or the cytoplasm

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月22日

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  • Allana Schooley,
  • Sergey V. Venev,
  • Vasilisa Aksenova,
  • Jesse W. Lehman,
  • Emily Navarrete,
  • Athma A. Pai,
  • Mary Dasso,
  • Job Dekker

摘要

Identity-specific chromosome conformation must be re-established at each cell division. To uncover how interphase folding is inherited, we developed an approach that segregates chromosome-intrinsic mechanisms from those propagated through the cytoplasm during G1 nuclear reassembly. Inducible degradation of proteins essential for the establishment of nucleocytoplasmic transport during mitotic exit enabled analysis of folding programmes with distinct modes of inheritance. Here we show that genome compartmentalization is driven entirely by chromosome-intrinsic factors. In addition to conventional compartmental segregation, the chromosome-intrinsic folding programme leads to prominent genome-scale microcompartmentalization of mitotically bookmarked cis-regulatory elements. The microcompartment conformation forms transiently during telophase and is subsequently modulated by a second folding programme inherited through the cytoplasm in early G1. This programme includes cohesin-mediated loop extrusion and factors involved in transcription and RNA processing. The combined and interdependent action of chromosome-intrinsic and cytoplasmic inherited folding programmes determines the interphase chromatin conformation as cells exit mitosis.