6t7c
From Proteopedia
Structure of two copies of human Sox11 transcription factor in complex with a nucleosome
Structural highlights
Disease[SOX11_HUMAN] Coffin-Siris syndrome. The disease is caused by mutations affecting the gene represented in this entry. Function[H2B1K_HUMAN] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid. [SOX11_HUMAN] Transcription factor that acts as a transcriptional activator (PubMed:24886874). Binds cooperatively with POU3F2/BRN2 or POU3F1/OCT6 to gene promoters, which enhances transcriptional activation (By similarity). Acts as a transcriptional activator of TEAD2 by binding to its gene promoter and first intron (By similarity). Plays a redundant role with SOX4 and SOX12 in cell survival of developing tissues such as the neural tube, branchial arches and somites, thereby contributing to organogenesis (By similarity).[UniProtKB:Q7M6Y2][1] Publication Abstract from PubMed'Pioneer' transcription factors are required for stem-cell pluripotency, cell differentiation and cell reprogramming(1,2). Pioneer factors can bind nucleosomal DNA to enable gene expression from regions of the genome with closed chromatin. SOX2 is a prominent pioneer factor that is essential for pluripotency and self-renewal of embryonic stem cells(3). Here we report cryo-electron microscopy structures of the DNA-binding domains of SOX2 and its close homologue SOX11 bound to nucleosomes. The structures show that SOX factors can bind and locally distort DNA at superhelical location 2. The factors also facilitate detachment of terminal nucleosomal DNA from the histone octamer, which increases DNA accessibility. SOX-factor binding to the nucleosome can also lead to a repositioning of the N-terminal tail of histone H4 that includes residue lysine 16. We speculate that this repositioning is incompatible with higher-order nucleosome stacking, which involves contacts of the H4 tail with a neighbouring nucleosome. Our results indicate that pioneer transcription factors can use binding energy to initiate chromatin opening, and thereby facilitate nucleosome remodelling and subsequent transcription. Nucleosome-bound SOX2 and SOX11 structures elucidate pioneer factor function.,Dodonova SO, Zhu F, Dienemann C, Taipale J, Cramer P Nature. 2020 Apr;580(7805):669-672. doi: 10.1038/s41586-020-2195-y. Epub 2020 Apr, 22. PMID:32350470[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Large Structures | Cramer, P | Dienemann, C | Dodonova, S O | Taipale, J | Zhu, F | Dna | Histone | Nuclear protein | Nucleosome | Pioneer factor | Sox11 | Transcription factor
