Genome Architecture Mapping, a New Single-Cell Approach to Map Chromatin Contacts


Identification: Pombo, Ana


Description

Genome ArchitectureMapping,a New Single-Cell Approach to Map Chromatin Contacts

Ana Pombo

Berlin Institute forMedical Systems Biology,Max DelbrueckCentre forMolecularMedicine, Berlin,Germany

GenomeArchitecture Mapping(GAM)is anovelligation-freemethodfor determining chromatininteractionsona genome-wide scale, whichis capableof detectingsimultaneousinteractionsbetweenthreeormore genomiclociatthesinglecelllevel.GAMcanbeapplieddirectlyon tissues, requiressmallnumberof cells, andpresents lowintrinsic bias. Wehavefirst appliedGAMto produceagenome-wide dataset of chromatininteractionsinmouse EScells. Weidentifypreferential chromatincontacts spanningtensof megabases,includingespecially prominentinteractionsbetweenactive genesandenhancer regions,andvalidatethese contacts by independentsingle-cellFISH experiments. By exploitingtheuniqueabilityofGAMtointerrogatehigh- multiplicityinteractions, we detectastrikingpatternof abundant, simultaneousthree-waycontactsgenome-wide. These“triplet”contacts includeinteractions betweenhighlytranscribedtopological domains (TADs)and/or TADscontainingsuper-enhancers.Ourworkindicates thatthesimultaneousassociationofmultipleregulatoryregionsislikely tobe animportantaspectof genomearchitecture.

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