Mechanisms for the Inheritance of Chromatin States.pdfVIP

Leading Edge PerspectiveMechanisms for the Inheritance of Chromatin States Danesh Moazed1,* 1Howard Hughes Medical Institute, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA *Correspondence: danesh@hms.harvard.edu DOI 10.1016/j.cell.2011.07.013 Studies in eukaryotes ranging from yeast to mammals indicate that specific chromatin structures can be inherited following DNA replication via mechanisms acting in cis. Both the initial establish- ment of such chromatin structures and their inheritance require sequence-dependent specificity factors and changes in histone posttranslational modifications. Here I proposemodels for themain- tenance of epigenetic information in which DNA silencers or nascent RNA scaffolds act as sensors that work cooperatively with parentally inherited histones to re-establish chromatin states following DNA replication.Cells with identical genomes can display distinct gene expres- sion patterns and phenotypes that persist during numerous cell divisions. This capacity is critical for cellular differentiation and for development of multicellular organisms with stable tissues, organs, and morphologies, all of which arise from a single founder cell, the fertilized egg. The distinct gene expres- sion and phenotypic states of genetically identical cells, which develop without change in DNA sequence and persist in the absence of initial inducing signals, are referred to as epigenetic states (Gottschling, 2004; Ringrose and Paro, 2004). Following establishment during embryogenesis, a variety of mechanisms mediate the epigenetic inheritance of gene expres- sion states. These mechanisms can be broadly divided into trans-acting and cis-acting. The first class relies on positive feed- back mechanisms involving diffusible regulatory factors and includes transcription factors, such as the phage lambda repressor (cI) and Cro proteins, and eukaryotic cell type-specific master regulators, such as the fungal Wor1 and mammalian myoD protein