Andrew J. Pospisilik
Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany
Epigenetic control of complex disease
Circadian gene-expression and function are a characteristic of virtually all cell types. Tightly synchronized circadian gene-expression on the organismal level is controlled by integration of nutrient, environment and behavioural inputs with periodic gene expression in the brain’s central pacemaker. These inputs combine to synchronize peripheral clocks found within all other cells of the body, and if disrupted, lead to multiple metabolic and behavioural anomalies including impaired cognitive function, poor regenerative capacity, hyperglycemia, and obesity. Circadian clocks comprise a group of ~10 core transcription factors whose negative feedback loops establish cyclical expression with a intrinsic period of ~24 hours. Critically, clock transcription factors integrate metabolic, transcriptional, and endocrine signals to modulate expression of hundreds of genes per tissue, so called CCG’s, or clock controlled genes. The result is that approximately 10-15% of genes in any given tissue exhibit circadian gene expression. Recent work has shown that chromatin modification effects a major portion of circadian transcriptional control. To date, the chromatin remodelers Sirt1 and HDAC3 (histone deacetylases), p300 (acetyltransferase), as well as the Polycomb/ Trithorax Group proteins Mll and Ezh2 (H3K4me3 and H3K27me3 methyltransferases respectively) have so far been implicated. Currently, the extent of circadian chromatin plasticity has yet to be defined for any tissue. As a new member of Epigenesys we propose to define a cursory circadian “epigenome” correlating chromatin accessibility with Mll/Ezh2 function and nutritional state in adipose tissue of the mouse. Samples will be subject to FAIRE-/DNAseI-seq, ChIP-seq for H3K4me3 and H3K27me3, as well as transcriptome and metabolome analysis and the data controlled using tissue-specific deletion mutants.
Thus, we will define
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An open call for bilateral Franco-German projects in human epigenomics from the ANR-France has been announced! The deadline to submit a "declaration of intention" is March 29th, 2013. Click here for the announcement (in French).
Edith Heard, named a Chair of the Collège de France in Epigenetics and Cellular Memory will be giving weekly lectures starting in February that, in the tradition of this great institution, are free for anyone to attend. Lectures (in French) are from 16-17:30…
Watch the Nobel Prize winner, Sir John Gurdon, speak about winning the prize and about his revolutionary work on nuclear reprogramming.