1998/01/01 by Alicia K. Michael, Ralph S. Grand, Luke Isbel +13 · 1 voice · 6 citations
Arts and Humanities · Biochemistry, Genetics and Molecular Biology · Social Sciences · #Basque language and culture studies #CRISPR and Genetic Engineering #Genomics and Chromatin Dynamics #Pluripotent Stem Cells Research #Spanish Linguistics and Language Studies #linguistics and terminology studies
paper · doi:10.1126/science.abb0074
openalex publication_date 1998/01/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/06/24
Transcription factors (TFs) regulate gene expression through chromatin where nucleosomes restrict DNA access. To study how TFs bind nucleosome-occupied motifs, we focused on the reprogramming factors OCT4 and SOX2 in mouse embryonic stem cells. We determined TF engagement throughout a nucleosome at base-pair resolution in vitro, enabling structure determination by cryo-electron microscopy at two preferred positions. Depending on motif location, OCT4 and SOX2 differentially distort nucleosomal DNA. At one position, OCT4-SOX2 removes DNA from histone H2A and histone H3; however, at an inverted motif, the TFs only induce local DNA distortions. OCT4 uses one of its two DNA-binding domains to engage DNA in both structures, reading out a partial motif. These findings explain site-specific nucleosome engagement by the pluripotency factors OCT4 and SOX2, and they reveal how TFs distort nucleosomes to access chromatinized motifs.