title: Analysis of a transgenic Oct4 enhancer reveals high fidelity long-range chromosomal interactions.
abstract: Genome structure or nuclear organization has fascinated researchers investigating genome function. Recently, much effort has gone into defining relationships between specific genome structures and gene expression in pluripotent cells. We previously analyzed chromosomal interactions of the endogenous Oct4 distal enhancer in pluripotent cells. Here, we derive ES and iPS cells from a transgenic Oct4 distal enhancer reporter mouse. Using sonication-based Circularized Chromosome Conformation Capture (4C) coupled with next generation sequencing, we determined and compared the genome-wide interactome of the endogenous and transgenic Oct4 distal enhancers. Integrative genomic analysis indicated that the transgenic enhancer binds to a similar set of loci and shares similar key enrichment profiles with its endogenous counterpart. Both the endogenous and transgenic Oct4 enhancer interacting loci were enriched in the open nucleus compartment, which is associated with active histone marks (H3K4me1, H3K27ac, H3K4me3 and H3K9ac), active cis-regulatory sequences (DNA hypersensitivity sites (DHS)), 5-hydroxymethylcytosine (5-hmc), and early DNA replication domains. In addition, binding of some pluripotency-related transcription factors was consistently enriched in our 4C sites, and genes in those sites were generally more highly expressed. Overall, our work reveals critical features that may function in gene expression regulation in mouse pluripotent cells.
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.|Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA 90033, USA.|Division of Biostatistics, Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Cai
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.|Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Gao
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Peilin
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Woojin
authors.initials: W
authors.lastname: An
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Jiandang
authors.initials: J
authors.lastname: Shi
authors.affiliation: Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA 90033, USA.|Division of Biostatistics, Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033, USA.|Department of Psychiatry, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.|Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Wange
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D002460:Cell Line; D033481:Chromosomes, Mammalian / Q000235:genetics; D018899:CpG Islands; D004261:DNA Replication; D004742:Enhancer Elements, Genetic; D004843:Epistasis, Genetic; D005786:Gene Expression Regulation; D057026:Induced Pluripotent Stem Cells / Q000502:physiology; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000502:physiology; D050814:Octamer Transcription Factor-3 / Q000235:genetics*
chemical_list: D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse