Open questions: Epigenetics and the role of heterochromatin in development
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
BMC Biology 2013, 11:21 doi:10.1186/1741-7007-11-21Published: 4 March 2013
First paragraph (this article has no abstract)
Over the last 8 years my laboratory has begun to explore the question of epigenetic changes during differentiation and development, and its link to nuclear organization, which indeed changes during cell differentiation. We developed a method to image chromatin domains in the living nematode Caenorhabditis elegans, because the worm provides opportunities to study the effects of nuclear organization on gene expression during well-characterized cellular differentiation events. We found that the nuclear localization of tissue-specific promoters, which seem to have no fixed positions in early embryos, shift within the nucleus during cell differentiation, so that they are positioned near the nuclear lamina when they are inactive, and are restricted to the center of the nucleus when expressed. This was true in four different cell types representing distinct cell lineages (muscle, gut, neurons and hypoderm) . The movement to the nuclear center coincided with transcriptional induction, but was not simply a result of transcription: active genes can be tethered to the nuclear envelope and stress-induced promoters, such as the heat-shock activated promoter hsp-16.2, actually bind the nuclear pore in their active state . We then identified lysine methylation on histone H3 lysine 9 (H3K9) as the critical signal for anchoring heterochromatin to the nuclear envelope. Not only tri-methylation, but apparently mono- and di-methylation as well, deposited by the sequential action of two histone methyl transferases (HMT) called MET-2 and SET-25, led to the sequestration of the modified chromatin at the nuclear envelope . A second, and very unexpected finding was that C. elegans embryos can develop into adult worms with the full range of differentiated tissues, without any histone H3K9 methylation (H3K9me) whatsoever.