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

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 () and Josephine C. Ferreon ()
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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
Kevin R. MacKenzie: Baylor College of Medicine
Allan Chris M. Ferreon: Baylor College of Medicine
Choel Kim: Baylor College of Medicine
Josephine C. Ferreon: Baylor College of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-25761-7

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