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

Sharma, Rajesh; Choi, Kyoung-Jae; Quan, My Diem; Sharma, Sonum; Sankaran, Banumathi; Park, Hyekyung; LaGrone, Anel; Kim, Jean J.; MacKenzie, Kevin R.; Ferreon, Allan Chris M.; Kim, Choel; Ferreon, Josephine C.

doi:10.1038/s41467-021-25761-7

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

Journal Article · Wed Sep 22 00:00:00 EDT 2021 · Nature Communications

DOI:https://doi.org/10.1038/s41467-021-25761-7· OSTI ID:1829469

Sharma, Rajesh ^[1]; Choi, Kyoung-Jae ^[1]; Quan, My Diem ^[1]; Sharma, Sonum ^[1];

^[2]; Park, Hyekyung ^[1]; LaGrone, Anel ^[1];

^[1]; MacKenzie, Kevin R. ^[1];

^[1];

^[1]

Baylor College of Medicine, Houston, TX (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

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.

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Research Organization:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH); Cancer Prevention and Research Institute of Texas

Grant/Contract Number:: AC02-05CH11231; R01 GM122763; R21 NS107792; R01 NS105874; R21 NS109678; RP160805; R01 DK121970; R61 HD099995; P30 GM124169-01; P30 CA125123; S10 OD028591

OSTI ID:: 1829469

Journal Information:: Nature Communications, Vol. 12, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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