title: Identifying functional neighborhoods within the cell nucleus: proximity analysis of early S-phase replicating chromatin domains to sites of transcription, RNA polymerase II, HP1gamma, matrin 3 and SAF-A.
abstract: Higher order chromatin organization in concert with epigenetic regulation is a key process that determines gene expression at the global level. The organization of dynamic chromatin domains and their associated protein factors is intertwined with nuclear function to create higher levels of functional zones within the cell nucleus. As a step towards elucidating the organization and dynamics of these functional zones, we have investigated the spatial proximities among a constellation of functionally related sites that are found within euchromatic regions of the cell nucleus including: HP1gamma, nascent transcript sites (TS), active DNA replicating sites in early S-phase (PCNA) and RNA polymerase II sites. We report close associations among these different sites with proximity values specific for each combination. Analysis of matrin 3 and SAF-A sites demonstrates that these nuclear matrix proteins are highly proximal with the functionally related sites as well as to each other and display closely aligned and overlapping regions following application of the minimal spanning tree (MST) algorithm to visualize higher order network-like patterns. Our findings suggest that multiple factors within the nuclear microenvironment collectively form higher order combinatorial arrays of function. We propose a model for the organization of these functional neighborhoods which takes into account the proximity values of the individual sites and their spatial organization within the nuclear architecture.
authors.affiliation: Department of Biological Sciences, University at Buffalo, Buffalo, New York 14260, USA.
authors.forename: Kishore S
authors.initials: KS
authors.lastname: Malyavantham
authors.forename: Sambit
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Marcos
authors.initials: M
authors.lastname: Barbeitos
authors.forename: Lopamudra
authors.initials: L
authors.lastname: Mukherjee
authors.forename: Jinhui
authors.initials: J
authors.lastname: Xu
authors.forename: Frank O
authors.initials: FO
authors.lastname: Fackelmayer
authors.forename: Ronald
authors.initials: R
authors.lastname: Berezney
mesh_terms: D000465:Algorithms; D002467:Cell Nucleus / Q000737:chemistry / Q000648:ultrastructure*; D002843:Chromatin / Q000737:chemistry* / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D053263:Gene Regulatory Networks; D006367:HeLa Cells; D006801:Humans; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D012319:RNA Polymerase II; D016601:RNA-Binding Proteins; D016196:S Phase; D014157:Transcription Factors; D014158:Transcription, Genetic
chemical_list: C453799:Cbx3 protein, mouse; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C518587:MATR3 protein, human; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein; D012319:RNA Polymerase II