CHROMATIN DOMAINS AND
INSULATORS
Baeza (Jaén, Spain), November 9-11, 2009
Organizers:
Department of Biology, Emory University, Atlanta, USA Instituto
de Fisiología Celular, Universidad Nacional Autónoma de México, DF, México Centro
Nacional de Biotecnología, CSIC, Madrid, Spain
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Organizers.
UNIA CURRENT
TRENDS IN BIOMEDICINE WORKSHOP
2009 ON:
(FINAL) October 19, 2009
SCOPE OF THE WORKSHOP
During the past years a number of genomes from different species, including various vertebrates and, among them, several mammalian species, have been completely sequenced. In general, one of the most surprising facts uncovered from the first series of analysis has been the proportion of "coding" versus "non-coding (for proteins)" genetic sequences and the relatively low number of genes or transcription units found.
The use of powerful bioinformatics approaches has allowed the identification of evolutionary conserved sequences that spread well beyond the coding regions and, thus, include regulatory elements that appear to transduce relevant functional and/or structural constraints that have been preserved in different species, presumably originating in the genome of a common ancestor.
Boundaries or insulators are a specific type of regulatory elements, first discovered in invertebrates (i.e. Drosophila) and lower eukaryotes (i.e. yeast) and later shown to be present in vertebrate genomes. These elements are characterised as possessing at least one of the following two features: to act as blockers, thereby preventing the communication and interaction between distal enhancers and proximal promoters; or to act as barriers, thereby preventing the spreading of negative heterochromatic effects originating in the chromosome that could compromise the expression of neighbouring loci. Some boundaries have been shown to contain both types of activities (blocker and barrier function) whereas other (i.e. in the yeast genome, working as barriers) have been reported to transduce one of the two functions.
Studies carried out with some of the best characterised boundary elements, such as the gypsy insulator of the Drosophila genome, suggest that besides a clear functional role (acting as barriers and/or blockers) boundary elements could also have a structural role, and therefore, contribute to the nuclear organisation. From these studies we know that expression loci are organised in the form of "chromatin domains" that remain insulated from neighbouring domains through the presence of boundary elements. These elements would then be instrumental for the specification of proper and internally coherent expression domains within chromosomes.
Some specific nuclear factors have been identified as the real transducers of boundary function. Most notably, CTCF, a large zinc-finger transcription factor, has been implicated in several insulators characterised in several species. Further, its binding sites in mammalian genomes have been investigated suggesting a variety of roles with a much higher complexity than ever anticipated. Alterations in CTCF function have been shown to affect nuclear processes such as X chromosome-inactivation in mammalian female cells, genomic imprinting or have been associated with tumorogenesis, revealing a role of CTCF also in the ethiology of some types of cancer.
The ability of insulators to shield a genomic sequence from surrounding loci has been exploited in gene transfer events. Reported boundary elements have been used to protect gene constructs included in viral vectors or transgenes from position effects. Results obtained suggest that the use of boundaries in gene transfer experimental approaches will greatly enhance the efficacy of constructs used for gene therapy and the robustness of transgenic constructs used in developmental biology-type of studies.
To date, several types of boundary elements have been identified. They share a common function but appear to be unrelated at the structural level therefore suggesting that, throughout the evolution, the system has been using different mechanisms that were available, probably established and/or fixed for other purposes, which have been adapted to suit the requirements of an insulator, that is: protecting a set of sequences from surrounding loci and thus allowing the internal regulatory elements to control the gene and avoiding other distal elements to alter the pattern of expression.
This workshop "Chromatin Domains and Insulators" will address and discuss the most updated knowledge of how chromatin is organised in the eukaryotic nucleus and what is the role of insulators in this process. World-wide recognised and leading scientists in the field have been considered, covering the different aspects in which this topic has been addressed in the recent literature. The workshop will cover from general descriptions of boundaries in vertebrate and invertebrate genomes, to more specific roles of boundaries in nuclear or cellular processes.
List of invited speakers (confirmed):
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about the UNIA workshop series "Current Trends in Biomedicine"
Where is Baeza? (google maps)
about Baeza (pictures by Lluís Montoliu)
Illustrations from Victor G. Corces lab web site
last updated: November 12, 2009