Long-distance Chromatin Mechanisms Controlling Tissue-specific Gene Locus Activation

Several different types of regulatory mechanisms contribute to the tissue- and development-specific regulation of a gene. It is now well established that, in addition to promoters, upstream cis-regulatory elements, which bind a variety of trans-acting factors, are essential for correct gene activation. In the last few years, however, it has become evident that the chromatin structure of eukaryotic genes is an important additional regulatory layer that is essential for correct gene expression during development. Chromatin is essentially a repressive environment for transcription factors; hence, much effort in recent years has been devoted to the elucidation of how these repressive forces are overcome during the process of gene locus activation. A particular interesting question in this context is: what are the molecular mechanisms by which extensive regions of chromatin, in many cases far outside the coding region, are reorganized during development? In this review, I summarize data from recent investigations that have uncovered a surprising variety of factors involved in this process.