title: Differential Nucleosome Occupancies across Oct4-Sox2 Binding Sites in Murine Embryonic Stem Cells.
abstract: The binding sequence for any transcription factor can be found millions of times within a genome, yet only a small fraction of these sequences encode functional transcription factor binding sites. One of the reasons for this dichotomy is that many other factors, such as nucleosomes, compete for binding. To study how the competition between nucleosomes and transcription factors helps determine a functional transcription factor site from a predicted transcription factor site, we compared experimentally-generated in vitro nucleosome occupancy with in vivo nucleosome occupancy and transcription factor binding in murine embryonic stem cells. Using a solution hybridization enrichment technique, we generated a high-resolution nucleosome map from targeted regions of the genome containing predicted sites and functional sites of Oct4/Sox2 regulation. We found that at Pax6 and Nes, which are bivalently poised in stem cells, functional Oct4 and Sox2 sites show high amounts of in vivo nucleosome displacement compared to in vitro. Oct4 and Sox2, which are active, show no significant displacement of in vivo nucleosomes at functional sites, similar to nonfunctional Oct4/Sox2 binding. This study highlights a complex interplay between Oct4 and Sox2 transcription factors and nucleosomes among different target genes, which may result in distinct patterns of stem cell gene regulation.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Amy
authors.initials: A
authors.lastname: Sebeson
authors.affiliation: Department of Statistics, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Liqun
authors.initials: L
authors.lastname: Xi
authors.affiliation: Department of Statistics, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Quanwei
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Audrey
authors.initials: A
authors.lastname: Sigmund
authors.affiliation: Department of Statistics, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Ji-Ping
authors.initials: JP
authors.lastname: Wang
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Widom
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D005136:Eye Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000378:metabolism*; D064231:Nestin / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000737:chemistry / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; C577485:Nes protein, mouse; D064231:Nestin; D009707:Nucleosomes; D050814:Octamer Transcription Factor-3; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; C494174:Pou5f1 protein, mouse; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse