Eukaryotes chromosomes are subdivided into functionally and structurally autonomous domains. While this was first suggested by cytological studies on the lampbrush chromosomes of amphibian oocytes and the polytene chromosomes of insects more than a half century ago, only little progress was made on this problem until 10-15 years ago. Since then a combination of genetic, molecular and biochemical experiments has provided convincing evidence for the domain organization of eukaryotic chromosomes. These studies have shown that the domain organization of the chromatin fiber is of critical importance not only for the packaging of chromosomes inside the nucleus, but also for the proper regulation of gene activity. The subdivision of eukaryotic chromosome into discrete domains requires a mechanism to separate one domain from another. Special elements called boundaries or insulators have been shown to serve this purpose. Elements that function as boundaries of chromatin domains were first identified in Drosophila, and they have now been found in a diverse array of organisms including from yeast to mammals. These elements delimit high order chromatin domains and function to establish independent units of gene activity, insulating genes or regulatory elements within a domain from the action of regulatory elements located outside in adjacent domains. The major aims of this proposal are to learn more about the biological functions of boundaries, to characterize the factors that confer insulator activity of several BX-C boundaries (including apparent stage and perhaps tissue specific factors) and to elucidate the mechanisms that enable boundaries to establish independent units of genetic activity.

Public Health Relevance

Narrative Boundary elements subdivided eukaryotes chromosomes into functionally and structurally autonomous domains. The major aims of this proposal are to learn more about the role of boundaries in development and elucidate the mechanisms that enable boundaries to establish independent units of genetic activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM043432-21
Application #
8303412
Study Section
Molecular Genetics B Study Section (MGB)
Program Officer
Carter, Anthony D
Project Start
1989-12-01
Project End
2014-01-31
Budget Start
2012-08-01
Budget End
2014-01-31
Support Year
21
Fiscal Year
2012
Total Cost
$410,108
Indirect Cost
$152,292
Name
Princeton University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Fujioka, Miki; Mistry, Hemlata; Schedl, Paul et al. (2016) Determinants of Chromosome Architecture: Insulator Pairing in cis and in trans. PLoS Genet 12:e1005889
Kyrchanova, Olga; Mogila, Vladic; Wolle, Daniel et al. (2015) The boundary paradox in the Bithorax complex. Mech Dev 138 Pt 2:122-32
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
Bieli, Dimitri; Kanca, Oguz; Requena, David et al. (2015) Establishment of a Developmental Compartment Requires Interactions between Three Synergistic Cis-regulatory Modules. PLoS Genet 11:e1005376
Bonchuk, Artem; Maksimenko, Oksana; Kyrchanova, Olga et al. (2015) Functional role of dimerization and CP190 interacting domains of CTCF protein in Drosophila melanogaster. BMC Biol 13:63
Erokhin, Maksim; Elizar'ev, Pavel; Parshikov, Aleksander et al. (2015) Transcriptional read-through is not sufficient to induce an epigenetic switch in the silencing activity of Polycomb response elements. Proc Natl Acad Sci U S A 112:14930-5
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
Aoki, Tsutomu; Wolle, Daniel; Preger-Ben Noon, Ella et al. (2014) Bi-functional cross-linking reagents efficiently capture protein-DNA complexes in Drosophila embryos. Fly (Austin) 8:43-51
Deshpande, Girish; Willis, Elinor; Chatterjee, Sandip et al. (2014) BMP signaling and the maintenance of primordial germ cell identity in Drosophila embryos. PLoS One 9:e88847
Xu, Shuwa; Tyagi, Sanjay; Schedl, Paul (2014) Spermatid cyst polarization in Drosophila depends upon apkc and the CPEB family translational regulator orb2. PLoS Genet 10:e1004380

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