Transcription factors and nuclear factors responsible of chromatin architecture are partners in the control of gene expression patterns when cell differentiation is triggered

GRACIELA PIWIEN PILIPUK

Montevideo

Workshop; International Workshop Nuclear Architecture, Chromosome Territories, Chromatin Dynamics and Genetic Damage; 2011

Departamento de Antropología y Genética Humana de la Universidad Ludwig-Maximilians de Munich, Alemania , y Instituto de Investigaciones Biológicas Clemente Estable de Montevideo, Uruguay

How is gene expression integrated into the architectural framework of the cell nucleus? The genome is spatially organized. Individual chromosomes are non-randomly organized and occupy discrete patches in the nucleus referred to as chromosome territories separated by interchromosomal domains. The “interchromosome domain” model predicts that actively transcribed genes will be preferentially located at the surface of chromosome territories thus accessible to transcription. However, immunolabeling of nascent BrU-labeled RNA together with chromosome territory painting revealed that RNA transcripts can also be found throughout the interior of chromosome territories. Active genes can also be observed outside the chromosome territory. Cellular differentiation is achieved by keeping a specific subset of genes in a context where they can potentially be expressed whereas the rest is silenced. These highly regulated reciprocal events are hallmarks of mammalian organogenesis. The eukaryotic nucleus is functionally divided into heterochromatin compartments (highly condensed chromatin) that act mainly, although not exclusively, to silence gene transcription, and euchromatin compartments (decondensed chromatin) in which transcription is permitted. In addition to changes in chromatin structure, the nuclear microenvironment within which a chromosome is located could affect its gene regulation, and it has been proposed that whole chromosomes or part of them can shift their position in the nucleus for clusters of genes to share “transcription factories”. It is a challenge to understand at the molecular level how the architecture of the undifferentiated cell nucleus may gradually “accommodate” as the cells make their fate decision.  During the lecture we will discuss what we know and highlight many key questions for what we do not have an answer yet.