Current models for the higher order organization of eukaryotic chromosomes have suggested that the DNA-chromatin fiber is organized into a series of looped domains. A critical feature of the model are the nucleoprotein structures at the boundaries of each loop which organize the chromatin fiber into discrete domains. We have identified and characterized a novel class of chromatin structures, called scs, which appear to correspond to boundaries of higher chromosomal domains. We have shown that the scs- structures provide in vivo sites of action for topo II under circumstances where the topology of the domain is altered by gene activation/de- activation. We have also shown that the scs-structures can insulate against position effects, and will function to block the activity of nearby enhancer elements. The primary goals of the experiments proposed here are 1) to identify and characterize proteins which bind to scs DNA segments in vitro, 2) demonstrate that these proteins are associated with scs in vivo, and that this association is important for scs function, 3) characterize the scs nucleoprotein complex in detail, and 4) develop genetic strategies for analyzing how the scs protein complex functions in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM043432-02
Application #
3302473
Study Section
Molecular Biology Study Section (MBY)
Project Start
1989-12-01
Project End
1994-11-30
Budget Start
1990-12-01
Budget End
1991-11-30
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Princeton University
Department
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Fedotova, Anna; Aoki, Tsutomu; Rossier, Mikaël et al. (2018) The BEN Domain Protein Insensitive Binds to the Fab-7 Chromatin Boundary To Establish Proper Segmental Identity in Drosophila. Genetics 210:573-585
Lomaev, Dmitry; Mikhailova, Anna; Erokhin, Maksim et al. (2017) The GAGA factor regulatory network: Identification of GAGA factor associated proteins. PLoS One 12:e0173602
Cleard, Fabienne; Wolle, Daniel; Taverner, Andrew M et al. (2017) Different Evolutionary Strategies To Conserve Chromatin Boundary Function in the Bithorax Complex. Genetics 205:589-603
Chetverina, Darya; Fujioka, Miki; Erokhin, Maksim et al. (2017) Boundaries of loop domains (insulators): Determinants of chromosome form and function in multicellular eukaryotes. Bioessays 39:
Kaye, Emily G; Kurbidaeva, Amina; Wolle, Daniel et al. (2017) Drosophila Dosage Compensation Loci Associate with a Boundary-Forming Insulator Complex. Mol Cell Biol 37:
Kyrchanova, Olga; Zolotarev, Nikolay; Mogila, Vladic et al. (2017) Architectural protein Pita cooperates with dCTCF in organization of functional boundaries in Bithorax complex. Development 144:2663-2672
Kyrchanova, Olga; Mogila, Vladic; Wolle, Daniel et al. (2016) Functional Dissection of the Blocking and Bypass Activities of the Fab-8 Boundary in the Drosophila Bithorax Complex. PLoS Genet 12:e1006188
Fujioka, Miki; Mistry, Hemlata; Schedl, Paul et al. (2016) Determinants of Chromosome Architecture: Insulator Pairing in cis and in trans. PLoS Genet 12:e1005889
Wolle, Daniel; Cleard, Fabienne; Aoki, Tsutomu et al. (2015) Functional Requirements for Fab-7 Boundary Activity in the Bithorax Complex. Mol Cell Biol 35:3739-52
Bieli, Dimitri; Kanca, Oguz; Gohl, Daryl et al. (2015) The Drosophila melanogaster Mutants apblot and apXasta Affect an Essential apterous Wing Enhancer. G3 (Bethesda) 5:1129-43

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