Exploring and explaining epigenetic effects

摘要: STEVEN HENIKOFF AND MARJORI A. MATZKE* steveh@muller.thcrc.org mmatzke@oeaw.ac.at HOWARD HUGIfES MEDICAL INSTrlL'TE. FRED Ht~CHfNSOX CAXCER RLSEAaCH CENTER, 1100 FAIR',IP~," AVENtSE N0.tm[, SEATrLE, WA 98109-1024, USA. *[NSq'ITUq'E OF MOLECULAR BIOLOGY, AUS'IXlAN ACADE.',IY SCIENCES, BILLROTH~,TI~SSE 11, A-5~20 SALZBURG, Acs'rRIA. Epigenetic phenomena in diverse or- ganisms comprise some of the most intriguing and actively investigated problems genetics. The term 'epi- genetics' was introduced by Conrad Waddington to describe changes gene expression during develop- ment I. Nowadays, epigenetics sense refers alterations without a change nudeotide sequence. However, this definition is so broad that an issue Trends Genetics devoted epigen- etics would read more like modem biology textbook than series criti- cal reviews. A focused descrip- tion modifi- cations are brought about heritable, but poten- tially reversible, chroma- tin structure and/or DNA methylation. This explores both old new epigenetic phenomena, such as paramutation genomic imprinting, respectively. Although no consensus has yet emerged source etic effects, common threads connect- ing many suggest us host responses mobile elements provide unifying theme. In applied research, reac- tions invasive might be provoked genetic transformation, causing methylation-associated silencing can frustrate attempts engineer plants animals geneti- cally. Altered also consequence processes do not involve nuclear inheritance. Cosuppression post-transcriptional phe- nomenon due primarily en- hanced cytoplasmic turnover trans- homologous endogenous RNAs (Ref. 2). co- suppression been de- tected animal cells, phenom- enon 'quelling' Neurospora provides parallel (E.U. Selker, issue). Prims represent form inheritance involving heritable state (in case, protein conformation) 3 , behavior clearly demarcated from cases inheri- tance (J.B. Hollick, J.E. Dorweiler V.L. Chandler, effects usually silencing. any differentiated cell, genes normally in- active molecular components involved generating maintaining being discovered studying yeast Drosophila. yeasts, where powerful biochemical approaches combined, study mating type silencing, telomeric- centromeric-position al- lowed thorough analysis individ- ual constituents multiprotein com- plexes establish silenced state. New at several loci have indicated these classical only tip iceberg. dynamics including pro- tein modifications dur- cell cycle, account for much recent excitement field (J.M. Sherman L. Pillus, Drosophila it possible investigate complexes context well-studied developmental path- ways. There dozens genetically identified proteins ,:ilencing same target genes. These heterogeneous interact composite binding sites nucleate formation silenc- encompassing nearby sequences. 'stickiness' required occur operate between homologs even be- tween unlinked (V. Pirrotta, thb general model ability hetero- chromatin silence reporter genes, phenomenon known position effect variegation (PEVE organisms, associated with repeated Heterochromatin higher 'riG AUGUST 1997 VOL. 13 NO. 8 eukaryotes comprises types repeats, simple sequence arrays inactive elements. However filamentous fungi, repeti- tive sequences almost nonexist- ent owing occurrence two processes, RIP (repeat-induced point mutation) MIP (methylation- induced premeiotically). Linked duplications modified, epigenetically MIP. play genome defense roles because they brief period sexual cycle vegetative growth. Mobile likely natural targets ~lker, Fungi nomena resemble those seen . ukatyotes. For example, meiotic tmtsvection normal regulatory process takes place at'ross homologsS, similar numerous examples transvection mutant alleles Furthermore, states meiotically inherited fission 6.7 observed plants, which involves meintically weakening one allele other after their interaction heterozygote. Such befit- abflity hallmark plant ob- served post-transcriptienal cosuppression. Paramutation fascinating demonstrates tram, resulting persistent ex- pression interacting separately progeny. Para- mutation thus transgresses Mendel's first law, disallows residual influences on following segregation into different gametes. Initially believed affect few previously imagined. Recent include