Cell Death Differ,
Thanks to the Nobel Foundation for permission to publish this Lecture (Copyright((c)) The Nobel Foundation 2006). Here we report the transcript of the lecture delivered by Professor Craig C Mello at the Nobel Prize ceremony. Professor Mello vividly describes the years of research that led to the discovery of RNA interference and the molecular mechanisms that regulate this fundamental cellular process. The turning point of discoveries and the role played by all his colleagues and collaborators are described, making this a wonderful report of the adventure of research. The lecture explains in simple language the importance of this discovery that has added a great level of complexity to the way cells regulate protein levels; moreover, it points out the beauty and importance of Caenorhabditis elegans as a model organism and how the use of this model has greatly contributed to the advance of science. Finally, Professor Mello leaves us with a number of questions that his research has raised and that will require years of future research to be answered.Cell Death and Differentiation (2007) 14, 2013-2020; doi:10.1038/sj.cdd.4402252.
Chromatin is not randomly positioned in the nucleus, but is distributed in subdomains based on its degree of compaction and transcriptional status. Recent studies have shed light on the logic of chromatin distribution, showing that tissue-specific promoters drive distinct patterns of gene positioning during cell-type differentiation. In addition, the sequestration of heterochromatin at the nuclear envelope has been found to depend on lamin and lamin-associated proteins. On the chromatin side, H3K9 monomethylation, dimethylation and trimethylation were shown to be the critical signals for perinuclear anchoring in worm embryonic nuclei. Downregulation of an equivalent histone methyltransferase, G9a, in human cells has a similar effect. In worms, the sequestration of the terminal methyltransferase by repressed chromatin may facilitate the propagation of a heterochromatin compartment, much as the sequestration of the silent information regulatory complex does at telomeric foci in budding yeast. These results argue for conserved logic in eukaryotic nuclear organization.