Whole-genome analysis of chromatin structure and function.
The main goal of our laboratory is to understand how gene expression programs in higher eukaryotes are regulated. In particular, we focus on mechanisms of chromatin-mediated gene regulation in the living cell, in the context of the entire genome. Using Drosophila and mammalian cells as model systems, we develop and apply new whole-genome approaches to study the structure and composition of chromatin and the mechanisms of gene regulation.
Over the past years, we developed a novel technique (named “DamID”) for the genome-wide mapping of in vivo target loci of chromatin proteins and transcription factors. This microarray-based method allows us to test thousands of genomic sequences for in vivo binding of a chromatin protein or transcription factor of interest. We now routinely use DamID to generate whole-genome maps of protein binding in Drosophila and mammalian cell lines. These binding maps provide a wealth of new insights into the roles of each protein in determining chromatin structure and gene regulation. Among others, we and our collaborators have recently generated detailed binding maps of heterochromatin proteins, Polycomb proteins, nuclear envelope proteins, transcription factors, and other chromatin-associated proteins in Drosophila cells, and of heterochromatin proteins in human and mouse cells.
Gradually, we are building a large database of genome-wide binding maps of chromatin proteins and other regulatory proteins. An integral part of this research is the development and use of new bioinformatics approaches to analyze the large datasets that we generate. We employ algorithms for integration of our data with information from various biological databases, and for the discovery of global patterns in whole-genome data sets. These bioinformatics approaches allow us to gain insight into the global organization of chromatin and the architecture of regulatory networks.
Vogel M, Guelen L, de Wit E, Peric Hupkes D, Lodén M, Talhout W, Feenstra M, Abbas B, Classen AK, van Steensel B. (2006) Human heterochromatin proteins form large domains containing KRAB-ZNF genes. Genome Res. Epub ahead of print.
Tolhuis B, de Wit E, Muijrers I, Teunissen H, Talhout W, van Steensel B*, van Lohuizen M*. (2006) Genome-wide profiling of PRC1 and PRC2 Polycomb chromatin binding in Drosophila melanogaster. Nat Genet. 38(6):694-699.
Pickersgill H, Kalverda B, de Wit E, Talhout W, Fornerod M*, van Steensel B*. Characterization of the Drosophila melanogaster genome at the nuclear lamina. Nat Genet. 2006;38:1005-1014.
Moorman C, Sun LV, Wang J, de Wit E, Talhout W, Ward LD, Greil F, Lu XJ, White KP*, Bussemaker HJ*, van Steensel B*. (2006) Hotspots of transcription factor colocalization in the genome of Drosophila melanogaster. Proc Natl Acad Sci U S A. 103:12027-12032.
van Steensel B. (2005) Mapping of genetic and epigenetic regulatory networks using microarrays. Nat Genet.37 Suppl:S18-24.
More publications by Bas van Steensel on PubMed
Bas van Steensel received his Ph.D. in 1995 from the University of Amsterdam, where he studied the role of nuclear organization in gene regulation by steroid receptors. He worked as a postdoctoral fellow in the laboratory of Dr. Titia de Lange at the Rockefeller University (New York, NY, USA), where he elucidated some of the functions of the human telomere-binding proteins TRF1 and TRF2. In 1998 he joined the laboratory of Dr. Steven Henikoff at the Fred Hutchinson Cancer Research Center (Seattle, WA, USA), where he developed a new technique for whole-genome mapping of in vivo protein-DNA interactions. In 2000 he received a fellowship from the Netherlands Academy of Sciences and started a research group at the University of Amsterdam. In 2002 he joined the Netherlands Cancer Insitute, where his laboratory continues to develop and apply new genomics methodologies to analyze the structure and regulatory functions of chromatin.
Alexey Pindyurin PhD Postdoctoral Fellow
Guillaume Filion PhD Postdoctoral Fellow
Mario Amendola PhD Postdoctoral Fellow
Carolyn de Graaf PhD Postdoctoral Fellow
Jop Kind PhD Postdoctoral Fellow
Ludo Pagie PhD Bioinformatician
Joke van Bemmel MSc Graduate student
Joris van Arensbergen Postdoctoral Fellow
Tao Chen MSc Graduate student
Aranxta Rosado Technician
Marcel de Haas Technician
Sandra de Vries Technician