Afundamentaldistinctionamongthethreedomainsoflife—Archaea,BacteriaandEukaryota—isinhowtheirgenomesarepackaged.Inallthreelineages,highlybasicpackagingproteinshaveevolvedtoneutralizetheacidicphosphatesofDNA,althoughtheresultantdegreeofcompactiondiffersprofoundly.BacterialgenomesarelooselypackagedbyHUproteinsorotherbasicnucleoid-associatedproteins1.Bycontrast,archaealgenomesorganizeDNAwithsmallDNA-bindingpro-teinsorwrapDNAaroundanucleosomalparticlecon-sistingofatetramerofhistoneproteins2.Eachhistonecontainsahistone-folddomain,whichiscomposedofthreehelicesandservesasbothaproteindimerizationandDNA-bindingmodule3.Theemergenceofeukary-otescoincidedwithadoublingofthenumberofhistonesubunitsinanucleosome,withDNAspirallingleft-handed1.7timesaroundthehistoneoctamercore.Corehistonesbecamedifferentiatedfromas-yetunknownarchaeal-likeancestorsintothefamiliesH2A,H2B,H3andH4,inwhichacentral(H3–H4)2tetramerisflankedaboveandbelowbydimersofH2A–H2B4.ThisdoublingoftheDNAaroundthehistonecorerelativetoarchaealnucleosomesenabledthetightlevelofcompactionofchromatininmitoticchromosomes,whichisauniquefeatureofeukaryotes.TheH1linkerhistoneproteins,whichdifferfromotherhistonesinhavingaglobu-lardomaininsteadofahistone-folddomain,interactdirectlywithDNAmoleculesenteringandexitingthenucleosometomodulateitsaccessibility5.Histonegenesaregenerallypresentinmultiplecopies,andtheirexpressionistightlyregulatedatmul-tiplelevels6,7.Inanimals,so-calledcanonicalhistonegenesareclusteredandtranscribedonlyinSphase.ThemRNAslackintronsandthepolyAtailisreplacedwithaspecialstem–loopstructurethatregulatestheirprocessingandstimulatestranslation7.Eukaryoticcorehistoneshavefurtherdifferentiatedintoadditionalpara-logues,orvariants,thatfunctioninmultipleprocesses,includingtranscription,chromosomesegregationandDNArepair8.ThesynthesisanddepositionofcanonicalhistonesinanimalsandplantsarecoupledtoDNAsyn-thesis,wherebycanonicalhistonesassembleintonucleo-somesbehindthereplicationforkandatsitesofDNArepair.Bycontrast,thein...
