University of California, Berkeley
Department of Molecular & Cell Biology
163 Life Sciences Addition, #3200
Berkeley, CA 94720-3200
We are interested in systems analysis of the mechanisms of development in Drosophila and closely related insects. There are two related directions: (i) sequence analysis of transcription regulatory regions and (ii) quantitative modeling of spatio-temporal gene networks in Drosophila.
Major object is a group of early developmental genes, activated before gastrulation and involved into specification of germ layers (mesoderm, ectoderm etc) and presumptive segments. Formally, one can subdivide early developmental genes into two groups comprising Anterior-Posterior (AP) and Dorso-Ventral (DV) gene networks. Genes in the AP domain (gap and pair-rule) play central role in the embryo segmentation; genes in the DV domain (Dorsal target genes) are essential to specification of germ layers and cell types. Both AP and DV genes receive instructions from maternal determinants (such as transcription factors Bicoid or Dorsal), passed through the gene control regions – enhancers or cis-regulatory modules (CRMs). Often, enhancers occupy large portions of the gene loci, so they contain substantial amount of discrete sequence information. In response to the maternal instructions, the discrete sequence information unfolds into the continuous information of spatial gene expression patterns (stripes), specifying future body parts.
Exact mechanisms of the enhancer response to the maternal instructions are not clear; little is known about integration of inputs from multiple enhancers at the level of gene; reasons behind robustness of large developmental gene networks are even more obscure.
Zinzen, R.P. and D. Papatsenko, Enhancer Responses to Similarly Distributed Antagonistic Gradients in Development. submitted.
Zinzen, R.P., J. Cande, M. Ronshaugen, D. Papatsenko, and M. Levine, Evolution of the Ventral Midline in Insect Embryos. Dev Cell., 2006. to appear.
Zinzen, R.P., K. Senger, M. Levine, and D. Papatsenko, Computational models for neurogenic gene expression in the Drosophila embryo. Curr Biol., 2006. 16(13): p. 1358-65.
Papatsenko, D., ClusterDraw web server: a tool to identify and visualize clusters of binding motifs for transcription factors. submitted.
Papatsenko, D., A. Kislyuk, M. Levine, and I. Dubchak, Conservation patterns in different functional sequence categories of divergent Drosophila species. Genomics., 2006. 88(4): p. 431-42.
Boeva, V., M. Regnier, D. Papatsenko, and V. Makeev, Short fuzzy tandem repeats in genomic sequences, identification, and possible role in regulation of gene expression. Bioinformatics., 2006. 22(6): p. 676-84.
Papatsenko, D. and M. Levine, Quantitative analysis of binding motifs mediating diverse spatial readouts of the Dorsal gradient in the Drosophila embryo. Proc Natl Acad Sci U S A., 2005. 102(14): p. 4966-71.
Papatsenko, D. and M. Levine, Computational identification of regulatory DNAs underlying animal development. Nat Methods., 2005. 2(7): p. 529-34.
Ochoa-Espinosa, A., G. Yucel, L. Kaplan, A. Pare, N. Pura, A. Oberstein, D. Papatsenko, and S. Small, The role of binding site cluster strength in Bicoid-dependent patterning in Drosophila. Proc Natl Acad Sci U S A., 2005. 102(14): p. 4960-5.
Nazina, A.G. and D.A. Papatsenko, Statistical extraction of Drosophila cis-regulatory modules using exhaustive assessment of local word frequency. BMC Bioinformatics., 2003. 4: p. 65.
Makeev, V.J., A.P. Lifanov, A.G. Nazina, and D.A. Papatsenko, Distance preferences in the arrangement of binding motifs and hierarchical levels in organization of transcription regulatory information. Nucleic Acids Res., 2003. 31(20): p. 6016-26.
Lifanov, A.P., V.J. Makeev, A.G. Nazina, and D.A. Papatsenko, Homotypic regulatory clusters in Drosophila. Genome Res., 2003. 13(4): p. 579-88.
Clyde, D.E., M.S. Corado, X. Wu, A. Pare, D. Papatsenko, and S. Small, A self-organizing system of repressor gradients establishes segmental complexity in Drosophila. Nature., 2003. 426(6968): p. 849-53.
Papatsenko, D.A., V.J. Makeev, A.P. Lifanov, M. Regnier, A.G. Nazina, and C. Desplan, Extraction of functional binding sites from unique regulatory regions: the Drosophila early developmental enhancers. Genome Res., 2002. 12(3): p. 470-81.