CellfatereprogrammingthroughengineeringofnativetranscriptionfactorsRalfJauch1,2Cellularreprogrammingusingcocktailsoftranscriptionfactors(TFs)affirmstheepigeneticanddevelopmentalplasticityofmammaliancells.ItdemonstratestheabilityofTFsto‘read’geneticinformationandtorewireregulatorynetworksindifferentcellularcontexts.SilencedchromatinisnotanimpedimenttothegenomeengagementbyectopicallyexpressedTFs.ReprogrammingTFshavebeenidentifiedindiversestructuralfamiliesthatlackshareddomainsorsequencemotifs.Interestingly,thereprogrammingactivityofnon-redundantparalogousTFscanbeswitchedwithafewpointmutations.Thesefindingsrevealedthatthesequence–functionrelationshipsinfluencingreprogrammingaretiedtosubtlefeaturesdirectinggenomewidebinding.Therefore,endogenousreprogrammingTFsareamenabletodirectedbiomolecularengineeringthatopensupnewavenuestooptimizecellfateconversions.Addresses1GenomeRegulationLaboratory,CASKeyLaboratoryofRegenerativeBiology,JointSchoolofLifeSciences,GuangzhouInstitutesofBiomedicineandHealth,ChineseAcademyofSciences,Guangzhou510530,ChinaandGuangzhouMedicalUniversity,Guangzhou511436,China2SchoolofBiomedicalSciences,LiKaShingFacultyofMedicine,TheUniversityofHongKong,Pokfulam,HongKong,ChinaCorrespondingauthor:Jauch,Ralf(ralf@hku.hk)CurrentOpinioninGenetics&Development2018,52:109–116ThisreviewcomesfromathemedissueonCellreprogramming,regenerationandrepairEditedbyKnutWoltjenandAlexBortvinhttps://doi.org/10.1016/j.gde.2018.05.0130959-437X/ã2018ElsevierLtd.Allrightsreserved.IntroductionReprogrammingexperimentshavedemonstratedthatsmallsetsofTFsarecapableofactivatinggenesincellswheretheywouldotherwisebepermanentlysilenced.Asaconsequence,non-naturalcellstateconversionsoccurevenbetweencellsfromdistantdevelopmentaldomains.Thisdiscoveryshowedthatthespecificationsofcellfatesthatfollowtightlycontrolledhierarchicaltransitionsinvivoareinfactreversible.Reprogrammingassaysprovideapowerfultooltostudythesequence–structure–functionrelationshipsintranscriptionalcontrol.Specifically,...
