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Liquid condensation of reprogramming factor KLF4 with DNA provides a mechanism for chromatin organization

Author

Listed:
  • Rajesh Sharma

    (Baylor College of Medicine)

  • Kyoung-Jae Choi

    (Baylor College of Medicine)

  • My Diem Quan

    (Baylor College of Medicine)

  • Sonum Sharma

    (Baylor College of Medicine)

  • Banumathi Sankaran

    (Lawrence Berkeley National Laboratory)

  • Hyekyung Park

    (Baylor College of Medicine)

  • Anel LaGrone

    (Baylor College of Medicine)

  • Jean J. Kim

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Kevin R. MacKenzie

    (Baylor College of Medicine
    Baylor College of Medicine
    Baylor College of Medicine)

  • Allan Chris M. Ferreon

    (Baylor College of Medicine)

  • Choel Kim

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Josephine C. Ferreon

    (Baylor College of Medicine)

Abstract

Expression of a few master transcription factors can reprogram the epigenetic landscape and three-dimensional chromatin topology of differentiated cells and achieve pluripotency. During reprogramming, thousands of long-range chromatin contacts are altered, and changes in promoter association with enhancers dramatically influence transcription. Molecular participants at these sites have been identified, but how this re-organization might be orchestrated is not known. Biomolecular condensation is implicated in subcellular organization, including the recruitment of RNA polymerase in transcriptional activation. Here, we show that reprogramming factor KLF4 undergoes biomolecular condensation even in the absence of its intrinsically disordered region. Liquid–liquid condensation of the isolated KLF4 DNA binding domain with a DNA fragment from the NANOG proximal promoter is enhanced by CpG methylation of a KLF4 cognate binding site. We propose KLF4-mediated condensation as one mechanism for selectively organizing and re-organizing the genome based on the local sequence and epigenetic state.

Suggested Citation

  • Rajesh Sharma & Kyoung-Jae Choi & My Diem Quan & Sonum Sharma & Banumathi Sankaran & Hyekyung Park & Anel LaGrone & Jean J. Kim & Kevin R. MacKenzie & Allan Chris M. Ferreon & Choel Kim & Josephine C., 2021. "Liquid condensation of reprogramming factor KLF4 with DNA provides a mechanism for chromatin organization," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25761-7
    DOI: 10.1038/s41467-021-25761-7
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    Cited by:

    1. Tuan Nguyen & Sai Li & Jeremy T-H Chang & John W. Watters & Htet Ng & Adewola Osunsade & Yael David & Shixin Liu, 2022. "Chromatin sequesters pioneer transcription factor Sox2 from exerting force on DNA," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Wenmeng Wang & Dangdang Li & Qingqing Xu & Jiahui Cheng & Zhiwei Yu & Guangyue Li & Shiyao Qiao & Jiasong Pan & Hao Wang & Jinming Shi & Tongsen Zheng & Guangchao Sui, 2024. "G-quadruplexes promote the motility in MAZ phase-separated condensates to activate CCND1 expression and contribute to hepatocarcinogenesis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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