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Exploring the roles of RNAPII in genome organization

dc.contributor.advisorPapantonis, Argyris Prof. Dr.
dc.contributor.authorZhang, Shu
dc.date.accessioned2022-12-16T17:28:42Z
dc.date.available2022-12-23T00:50:09Z
dc.date.issued2022-12-16
dc.identifier.urihttp://resolver.sub.uni-goettingen.de/purl?ediss-11858/14426
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-9632
dc.format.extent123 Seitende
dc.language.isoengde
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.ddc570de
dc.titleExploring the roles of RNAPII in genome organizationde
dc.typedoctoralThesisde
dc.contributor.refereePapantonis, Argyris Prof. Dr.
dc.date.examination2022-12-06de
dc.description.abstractengThe role of RNAPII in 3D genome organization has been heavily debated over the last two decades. Here, in situ Hi-C and Micro-C data were used to conclusively address this debate. I discovered that: 1) using cell population in situ Hi-C data, longer loops with enhanced signal appear upon RNAPII depletion. Together with a rewired-loop pattern of gained loops in the absence of RNAPII, I can suggest that RNAPII may impede cohesin extrusion in human cells; 2) using in situ Hi-C data in G1-sorted cells, I observed loops with longer length, stronger signal, and stronger insulation, which are in line with the cell population in situ Hi-C data. Moreover, a diffuse signal pattern emerges upon RNAPII depletion in this data. Taken together, my data indicate RNAPII impeding cohesin extrusion in interphase. 3) using Micro-C data, transcription-level loops are captured, which show much weaker signal and insulation than CTCF loops. Moreover, on average, ~20% reduction in chromatin-bound CTCF and cohesin is seen in the absence of RNAPII. While this degree of loss does not affect loop detection in Micro-C maps, “transcription only” loops (especially enhancer-anchored loops) are severely weakened or lost in the absence of RNAPII. In addition, enhancer-bound cohesin is reduced by ~50%. Surprisingly, promoter-anchored loops are more stable than enhancer-anchored ones in the absence of RNAPII. Collectively, RNAPII is required for the formation of enhancer-anchored loops; and 4) using in situ Hi-C data from cells entering G1 after mitosis, ~20% reduction of chromatin-bound CTCF and cohesin is seen in the absence of RNAPII and loop formation is affected genome-wide during reentry into G1. Interestingly, as observed in Micro-C data, cohesin occupancy is reduced more at enhancers than promoters upon RNAPII degradation in this transition. Moreover, compartmentalization was also affected in the absence of RNAPII upon reentry G1. Thus, I can conclude that RNAPII is required to properly refold the genome during the mitosis to G1 transition.de
dc.contributor.coRefereeBeißbarth, Tim Prof. Dr.
dc.subject.eng3D genome organizationde
dc.subject.engRNAPII
dc.subject.engenhancer-promoter interactions
dc.subject.engloop extrusion
dc.identifier.urnurn:nbn:de:gbv:7-ediss-14426-3
dc.affiliation.instituteBiologische Fakultät für Biologie und Psychologiede
dc.subject.gokfullBiologie (PPN619462639)de
dc.description.embargoed2022-12-23de
dc.identifier.ppn1827750693
dc.identifier.orcid0000-0001-5784-9564de
dc.notes.confirmationsentConfirmation sent 2022-12-19T06:15:02de


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