Chromatin Structure/Boundary Elements
Research on chromatin structure focuses on the regulation of the homeotic Abd-B gene from BX-C. An elaborate cis-regulatory region is responsible for generating parasegment-specific expression of Abd-B. The region controls Abd-B expression in parasegments (PS)10-13 and is subdivided into 4 cis-regulatory domains: iab-5 (PS10), iab-6 (PS11), iab-7 (PS12) and iab-8 (PS13). Abd-B expression is divided into two phases: an initiation phase in which the gap and pair-rule segmentation genes activate the appropriate cis-regulatory domain and a memory phase in which Polycomb group and trithorax group genes maintain the parasegment specific cis-regulatory domains in the correct state, on or off. Each domain contains a unique set of initiator elements that respond to gap/pair-rule genes, and a set of maintenance elements that are targets for the Polycomb and trithorax group proteins. Critical to the functional autonomy of the cis-regulatory domains are chromatin boundary elements that insulate one domain from the adjacent domain. Studies underway are focused on one of the maintenance elements, the iab-7 Polycomb Response Element (PRE), and on two boundary elements Fab-7 and Fab-8 which flank the iab-7 cis-regulatory domain, insulating it from iab-7 and iab-8 respectively. Proteins that are critical for PRE or boundary function have been identified, and we are currently attempting to understand how these proteins contribute to either PRE or boundary activity. In related studies on chromatin structure we have shown that the zw5 gene encodes a protein component of the scs boundary. Multimerized binding sites for the Zw5 protein have boundary activity in vivo, and this activity is dependent on the zw5 gene.
Gregory Shanower- Postdoc
Tstomu Aoki - Postdoc
Daryl Gohl - Graduate Student
Deshpande, G., G. Calhoun, and P. Schedl, Drosophila argonaute-2 is required early in embryogenesis for the assembly of centric/centromeric heterochromatin, nuclear division, nuclear migration, and germ-cell formation. Genes Dev, 2005. 19(14): p. 1680-5.
Greenberg, A. J., J. L. Yanowitz, et al. (2004). "The Drosophila GAGA factor is required for dosage compensation in males and for the formation of the male-specific-lethal complex chromatin entry site at 12DE." Genetics 166(1): 279-89.
Mishra, R., Mihaly, J., Barges, S., Spierer, A., Karch, F., Hagstrom, K., Schweinsberg, S., and Schedl, P. (2000). The iab-7 Polycomb Response Element maps to a nucleosome free region of chromatin and requires both GAGA and Pleiohomeotic for silencing activity. Mol Cell Biol. 21 1311-8.
Barges, Mihaly, J., Galloni, M., Hagstrom, K., Müller, M., Shanower, G., Schedl, P., Gyurkovics, H., and Karch, F. (2000) The Fab-8 boundary defines the distal limit of the bithorax complex iab-7 domain and insulates iab-7 from initiation elements and a PRE in the adjacent iab-8 domain. Development, 127, 779-790.
Muller, M., Gyurkovics, H., Hagstrom, K., Pirrotta, V and Schedl, P. (1999). The Mcp element from the Drosophila melanogaster bithorax complex mediates long-distance regulatory interactions. Genetics. 153:1333-56.
Hagstrom, K., and Schedl, P. (1997). Remembrance of things past. Current Opinions in Genes and Development, 7:814-21.
Sipos, L., Mihaly, J., Karch, F., Schedl, P., Gausz, J. and Gyurkovics, H. (1997). Transvection in the Drosophila Abd-B domain estensive upstream sequence are involved in anchoring distant cis-regulatory regions to the promoter. Genetics, 149:1031-50.
Mihaly, J., Hogg, I., Barges, S., Galloni, M., Mishra, R.K., Hagstrom, K., Muller, M., Schedl, P., Sipos, L., Gausz, J., Gyurkovics, H., Karch, F., (1998). Chromatin domain boundaries in the Bithorax complex. Cell Mol Life Sci. 54:60-70.
Hagstrom, K., Müller, M., and Schedl, P. (1996). Fab 7 functions as a chromatin domain boundary to ensure proper segment specification by the Drosophila bithorax complex. Genes & Devel., 10:3202-3215.
Hagstrom, K., Müller, M., and Schedl, P. (1997). A Polycomb and GAGA dependent silencer adjoins the Fab 7 boundary in the Drosophila bithorax complex. Genetics, 146:1365-1380.
Bhat, K., G. Farkas, Karch, F., Gyurkovics, H., Gausz, J., and Schedl, P. (1996). The GAGA factor is required in the early Drosophila embryo not only for transcriptional regulation, but also for nuclear division. Development, 122:1113-1124.
Schedl, P., and F. Grosveld (1995). Domains and boundaries. In Chromatin Structure and Gene Expression. Editor - Sally Elgin. Oxford University Press.
Karch, F., M. Galloni, L. Sipos, J. Gausz, H. Gyurkovics, and P. Schedl (1994). mcp and Fab-7: Molecular analysis of putative boundaries of cis-regulatory domains in the bithorax complex of Drosophila melanogaster. Nucleic Acid Res., 22:3138-3146.
Vazquez, J., and P. Schedl (1994). Sequences required for enhancer blocking activity of scs are located within two nuclease-hypersensitive regions. EMBO J, 13:5984-5993.
Udvardy, A. and P. Schedl (1993). The dynamics of chromatin condensation: Redistribution of topoisomerase II in the 87A7 heat shock locus during induction and recovery. Mol. Cell Biol. 13:7522-7530.
Vazquez, J., G. Farkas, M. Gaszner, A. Udvardy, M. Muller, K. Hagstrom, H. Gyurkovics, L. Sipos, J. Gausz, M. Galloni, I. Hogga, F. Karch, and P. Schedl (1993). Genetic and molecular analysis of chromatin domains. Cold Spring Harbor Symposium in Quantitative Biology 58:45-54.
Galloni, M., H. Gyurkovics, P. Schedl and F. Karch (1993). The Bluetail transposon: Evidence for independent cis-regulatory domains and domain boundaries in the Bithorax complex. EMBO J., 12:1087-1097.
Kellum, R. and P. Schedl. (1992). A group of scs elements function as domain boundaries in an enhancer blocking assay. Mol. Cell Biol., 12:2424-2431.
Udvardy, A. and P. Schedl (1991). Chromatin structure, not DNA sequence specificity, is the primary determinant of topoisomerase II sites of action in vivo. Mol. Cell. Biol. 11:4973-4984.
Kellum, R. and P. Schedl (1991). A position effect assay for boundaries of higher order chromosomal domains. Cell, 64:941-950.