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Báo cáo khoa học: S1 – The genome in the 3rd millennium
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Epigenetic mechanisms, such as histone modifications, control eukaryotic development beyond DNA-stored information. Intrigu-ingly, there is an under-representation of repressive marks in quies-cent (resting) cells, stem cells and regenerating cells, but a selective accumulation of aberrant histone lysine methylation profiles in aging, ‘‘stressed’’ and tumor cells, particularly for the H3K9, H3K27 and H4K20 methyl marks. | S1 - The genome in the 3rd millennium BFEBS Journal Abstracts INVITED LECTURES - SYMPOSIA AREA S1 - The genome in the 3rd millennium S1.1 Coding and noncoding information in genome function S1.1.1 Epigenetic control by histone methylation T. Jenuwein Max Planck Institute of Immunobiology and Epigenetics Freiburg Germany - Epigenetic Focus Epigenetic mechanisms such as histone modifications control eukaryotic development beyond DNA-stored information. Intrigu-ingly there is an under-representation of repressive marks in quiescent resting cells stem cells and regenerating cells but a selective accumulation of aberrant histone lysine methylation profiles in aging stressed and tumor cells particularly for the H3K9 H3K27 and H4K20 methyl marks. To examine this notion in functional detail we have generated mutant mice that lack crucial HMTases such as e.g. the Suv39h and Suv4-20h enzymes. In addition we have been characterizing jumonjiC-containing proteins that represent histone lysine demethylases with the potential to remove H3K9me3 marks. We have also screened chemical libraries in collaboration with Boehringer Ingelheim Ridgefield USA and identified a small molecule inhibitor for the G9a HMTase. We have done extensive profiling by ChIP-chip micro-arrays for many histone modifications in chromatin from ES cells and from a variety of differentiated cells. Our data indicate that distinct histone lysine methylation profiles contribute to the epigenetic make-up of stem cells versus more committed cells. Surprisingly epigenetic variation appears to reside in repeat-associated heterochromatic islands and much less at annotated genes. Together these functional approaches promise to yield new insights into the plasticity of cell fate decisions and will provide novel strategies to modulate epigenetic control in normal and aberrant development. S1.1.2 Three-dimensional architecture of the human genome J. Dekker Program in Gene Function and Expression and Department of .