6vtx
Crystal structure of human KLF4 zinc finger DNA binding domain in complex with NANOG DNA
Structural highlights
FunctionKLF4_HUMAN Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription.[1] [2] Publication Abstract from PubMedExpression 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. Liquid condensation of reprogramming factor KLF4 with DNA provides a mechanism for chromatin organization.,Sharma R, Choi KJ, Quan MD, Sharma S, Sankaran B, Park H, LaGrone A, Kim JJ, MacKenzie KR, Ferreon ACM, Kim C, Ferreon JC Nat Commun. 2021 Sep 22;12(1):5579. doi: 10.1038/s41467-021-25761-7. PMID:34552088[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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