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

• Published in: Nature communications Vol. 12; no. 1; p. 5579
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 22.09.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Base Sequence; BASIC BIOLOGICAL SCIENCES; Binding sites; Cell differentiation; Cell Line; Cell Nucleus - metabolism; Cellular Reprogramming; Chromatin; Chromatin - metabolism; CpG islands; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA - genetics; DNA - metabolism; DNA Methylation; DNA-directed RNA polymerase; Domains; Enhancers; Epigenetics; Genomes; Humans; KLF4 protein; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors - chemistry; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Methylation; Models, Molecular; Mutation; Myc protein; Nanog Homeobox Protein - genetics; Nucleotide sequence; Oct-4 protein; Octamer Transcription Factor-3 - genetics; Pluripotency; Promoter Regions, Genetic; Protein Interaction Domains and Motifs; reprogramming; RNA polymerase; SOXB1 Transcription Factors - genetics; Topology; transcription; Transcription activation; Transcription factors; Zinc Fingers - genetics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-25761-7

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.