Wild chromatin: regulation of eukaryotic genes in their natural chromatin context.

Abstract

Nearly 40 years ago, Francois Jacob and Jacques Monod provided the first genetic evidence that genes are controlled through the opposing actions of activators and repressors on specific DNA targets. Although minimalistic, the classic paradigm provided by the regulation of the Lac operon in Escherichia coli quite accurately reflects the rationale of eukaryotic gene regulation, even in the context of highly organized chromosome structure. Transcriptional activation of most eukaryotic genes is now known to require several 10s of factors, many of which are responsive to developmental or environmental signaling pathways. Some regulators are enzymes that modify or reconfigure chromatin, whereas others influence the subnuclear organization of transcription factors or, in some cases, change the relative chromosomal environments of specific gene targets. Posttranslational modifications of histones or enhancer factors define localized chromatin domains as well as the activity and turnover of enhancer complexes. A crucial problem in the field now is to decipher how proper regulation springs from combinations of positive and negative factors, generally organized in multiprotein complexes or coupled to molecular engines, which recognize and modify regulatory loci embedded in chromatin. Remarkably, after an early period in which nucleosomal DNAwas seen as a negative and somehow passive template for transcription, chromatin and chromosome organization in the nucleus have now emerged as central parameters with direct and essential effects on the control of gene expression. The workshop “Regulation of Eukaryotic Genes in Their Natural Chromatin Context,” hosted by Fundacion Juan March in Madrid, Spain (April 22–24, 2002), was organized by Miguel Beato and Ken Zaret to address some of the most pressing issues concerning how complex regulatory networks work in their natural molecular environment: the chromosome.