title: Hierarchical regulation of the genome: global changes in nucleosome organization potentiate genome response.
abstract: Nucleosome occupancy is critically important in regulating access to the eukaryotic genome. Few studies in human cells have measured genome-wide nucleosome distributions at high temporal resolution during a response to a common stimulus. We measured nucleosome distributions at high temporal resolution following Kaposi's-sarcoma-associated herpesvirus (KSHV) reactivation using our newly developed mTSS-seq technology, which maps nucleosome distribution at the transcription start sites (TSS) of all human genes. Nucleosomes underwent widespread changes in organization 24 hours after KSHV reactivation and returned to their basal nucleosomal architecture 48 hours after KSHV reactivation. The widespread changes consisted of an indiscriminate remodeling event resulting in the loss of nucleosome rotational phasing signals. Additionally, one in six TSSs in the human genome possessed nucleosomes that are translationally remodeled. 72% of the loci with translationally remodeled nucleosomes have nucleosomes that moved to positions encoded by the underlying DNA sequence. Finally we demonstrated that these widespread alterations in nucleosomal architecture potentiated regulatory factor binding. These descriptions of nucleosomal architecture changes provide a new framework for understanding the role of chromatin in the genomic response, and have allowed us to propose a hierarchical model for chromatin-based regulation of genome response.
authors.affiliation: Department of Biological Science, The Florida State University, Tallahassee, Florida, USA.
authors.forename: Brittany S
authors.initials: BS
authors.lastname: Sexton
authors.affiliation: Department of Biological Science, The Florida State University, Tallahassee, Florida, USA.|Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Brooke R
authors.initials: BR
authors.lastname: Druliner
authors.affiliation: Department of Biological Science, The Florida State University, Tallahassee, Florida, USA.|The Center for Genomics and Personalized Medicine The Florida State University, Tallahassee, Florida, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Vera
authors.affiliation: Department of Biological Science, The Florida State University, Tallahassee, Florida, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Avey
authors.affiliation: Department of Biological Science, The Florida State University, Tallahassee, Florida, USA.
authors.forename: Fanxiu
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Biological Science, The Florida State University, Tallahassee, Florida, USA.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Dennis
mesh_terms: D002843:Chromatin / Q000235:genetics*; D045584:Chromosome Positioning; D002877:Chromosomes, Human / Q000235:genetics*; D005786:Gene Expression Regulation; D015894:Genome, Human / Q000235:genetics*; D006566:Herpesviridae Infections / Q000235:genetics* / Q000821:virology; D019288:Herpesvirus 8, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009707:Nucleosomes / Q000235:genetics*; D011485:Protein Binding; D014157:Transcription Factors; D024363:Transcription Initiation Site; D014775:Virus Activation / Q000235:genetics*
chemical_list: D002843:Chromatin; D009707:Nucleosomes; D014157:Transcription Factors
keywords: Chromosome Section; KSHV; chromatin; iSLK.219; next generation sequencing; nucleosome