An ambitious EC-funded research initiative on epigenetics advancing towards systems biology

States that biological species have evolved with 'modification by descent'. It is based on the observation that all species are built up of populations exhibiting natural variation, some of which is selected for because it enhances the fitness of an individual under a particular set of environmental conditions. Natural variation is generated by mutation whose degree and kind can be influenced by epigenetic traits.

The removal of acetyl groups (histone proteins in epigenetics). See also acetylation and epigenetic tag.

Process whereby cells/tissues become more specialized during embryonic development.

Deoxyribonucleic acid, the chemical molecule representing our genes and those of all other organisms. It is made up from a double-helically coiled sugar-phosphate backbone, held together by organic base pairs (adenine with thymine; guanine with cytosine). This generates two complementary strands of base-pairs. The entire sequence of the human genome contains billions of base-pairs.

The main types of chemical damage arise spontaneously from endogenous processes such as mitochondrial respiration leaking out oxygen radicals (superoxide and peroxides). These can cause oxidation, alcylation or hydrolysis of bases. At sites of base loss the deoxyribose residues exist in equilibrium between the closed furanose form and the open aldehyde form. The 3' phosphodiester bonds are readily hydrolyzed by a β-elimination reaction producing single-strand breaks. Further, double-strand breaks (i.e. two nearby single-strand breaks) can be caused by replication fork collapse, endonuclease activity and radiation. Some DNA repair proteins such as RecA, Rad50, Nbs1, Mre11 or Fen1 are among the most ancient proteins and may date back to the earliest replicators near the origin of life.

A reversible biochemical modification of DNA more or less universally present in organisms from bacteria to humans. Methyl groups can be enzymatically added to or removed from cytosine (C). Associated with silencing of DNA sequences.

DNA repair genes encode enzymes which fix DNA damage. Different repair genes function in homologous recombination or double-strand break (DSB) repair (e.g. RecA, Rad50/SMC complex) encompassing non homologous end joining (NHEJ), break-induced replication (BIR), single strand annealing (SSA) and Synthesis-Dependent Strand Annealing (SDSA). Further, in nucleotide excision repair (NER)(e.g. XPD), in base excision repair (BER)(e.g. TDG-glycosylase), mismatch repair (e.g. msh2), damage reversal (e.g. CPD photolyase), damage tolerance (e.g. Rad6), checkpoint-regulatory genes (e.g. RecQ helicases, Rad17, ATM, PARP), DNA polymerases and others like p53.

The process whereby a cell makes second identical copy of its DNA in preparation for cell division.

The sequence of bases in 5'->3' direction (printed left to right) along a strand of DNA. There are four organic bases, adenine (A), thymine (T), guanine (G) and cytosine (C) defining the sequence in a single strand DNA. The DNA sequence of a gene will determine the amino-acid composition of a protein.