Abstract

This proposal concerns the three dimensional arrangement and detailed structural organization of components within the cell nucleus. The nucleus is a complex organelle that contains, in the form of specific DNA sequences, the information needed for cell construction, maintenance, and replication. Although recent advances in molecular biology have revealed many of the details of gene structure and the decoding and transmission of genetic information, knowledge of the spatial framework within which these mechanisms operate has lagged behind. This is impeding a full understanding of the process of gene activation and control. Experiments are proposed to determine the three dimensional structures and spatial interrelationships within the nucleus. Electron microscopy will be combined with tomography and computer image processing to generate 3D reconstructions of nuclear components, with particular emphasis on the DNA- protein complex known as chromatin. Preparative methods shown to perturb the native structures as little as possible will be employed, and the work will be carried out using sources of nuclei that will be employed, and the work will be carried out using sources of nuclei that are most likely to reveal the basic structural principles of chromatin organization.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM043786-01
Application #
3302838
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1990-04-01
Project End
1996-12-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
University of Massachusetts Amherst
Department
Type
Schools of Arts and Sciences
DUNS #
153223151
City
Amherst
State
MA
Country
United States
Zip Code
01003

  Publications

Dechassa, Mekonnen Lemma; Zhang, Bei; Horowitz-Scherer, Rachel et al. (2008) Architecture of the SWI/SNF-nucleosome complex. Mol Cell Biol 28:6010-21
McBryant, Steven J; Krause, Christine; Woodcock, Christopher L et al. (2008) The silent information regulator 3 protein, SIR3p, binds to chromatin fibers and assembles a hypercondensed chromatin architecture in the presence of salt. Mol Cell Biol 28:3563-72
Woodcock, Christopher L; Skoultchi, Arthur I; Fan, Yuhong (2006) Role of linker histone in chromatin structure and function: H1 stoichiometry and nucleosome repeat length. Chromosome Res 14:17-25
Fan, Yuhong; Nikitina, Tatiana; Zhao, Jie et al. (2005) Histone H1 depletion in mammals alters global chromatin structure but causes specific changes in gene regulation. Cell 123:1199-212
Grigoryev, Sergei A; Nikitina, Tatiana; Pehrson, John R et al. (2004) Dynamic relocation of epigenetic chromatin markers reveals an active role of constitutive heterochromatin in the transition from proliferation to quiescence. J Cell Sci 117:6153-62
Nikitina, Tatiana; Woodcock, Christopher L (2004) Closed chromatin loops at the ends of chromosomes. J Cell Biol 166:161-5
Francis, Nicole J; Kingston, Robert E; Woodcock, Christopher L (2004) Chromatin compaction by a polycomb group protein complex. Science 306:1574-7
Fan, Yuhong; Nikitina, Tatiana; Morin-Kensicki, Elizabeth M et al. (2003) H1 linker histones are essential for mouse development and affect nucleosome spacing in vivo. Mol Cell Biol 23:4559-72
Springhetti, Evelyn M; Istomina, Natalia E; Whisstock, James C et al. (2003) Role of the M-loop and reactive center loop domains in the folding and bridging of nucleosome arrays by MENT. J Biol Chem 278:43384-93
Georgel, Philippe T; Horowitz-Scherer, Rachel A; Adkins, Nick et al. (2003) Chromatin compaction by human MeCP2. Assembly of novel secondary chromatin structures in the absence of DNA methylation. J Biol Chem 278:32181-8

Showing the most recent 10 out of 29 publications