"Epigenetics is a new frontier in biology. It has yielded revolutionary insight into how the genome works, and has profound implication for human health.This project focuses on the best-established epigenetic mark, DNA methylation. This mark is essential for the embryonic development and adult life of mammals, and acts primarily by regulating gene expression.While the essential functions of DNA methylation are well-known, our knowledge of its effectors is very limited. Nine mammalian proteins are known to recognize methylated DNA and regulate gene expression, but each has so far been studied in isolation, and on a very small portion of the genome.We want to describe the full landscape of DNA methylation in human cells by studying all 9 known proteins in parallel in a unified experimental system, using genome-wide approaches. Briefly, all proteins will be used in chromatin- immunoprecipitation followed by massive sequencing (ChIP-SEQ), in the human cell line K562. We will validate the identified patterns by directed approaches, submit them to an extensive bio-informatic analysis, and compare them to the distribution of DNA methylation, modified histones, transcription factors, and cofactors that have been and are being identified in this cell line. Biological hypotheses will be drawn from the results and tested experimentally in K562 and in non-transformed cells.Our data will yield the first integrated view of DNA methylation, its targets, and its effectors, in human cells, and will provide a quantum leap over the existing state of the art. The project will advance basic research, and will also likely prove useful in medicine."