Zur Kurzanzeige

Systematic analysis of heterochromatin modification readout

dc.contributor.advisorFischle, Wolfgang Prof. Dr.
dc.contributor.authorZimmermann, Nadin
dc.date.accessioned2017-06-14T08:46:55Z
dc.date.available2017-06-14T08:46:55Z
dc.date.issued2017-06-14
dc.identifier.urihttp://hdl.handle.net/11858/00-1735-0000-0023-3E76-7
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-6345
dc.language.isoengde
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc572de
dc.titleSystematic analysis of heterochromatin modification readoutde
dc.typedoctoralThesisde
dc.contributor.refereeFischle, Wolfgang Prof. Dr.
dc.date.examination2016-06-15
dc.description.abstractengModifications of the building units of chromatin - the histone proteins and DNA - direct the functional readout of the genome and are part of the so called “epigenome” (Fischle et al., 2003b; Kouzarides, 2007). Several studies have shown that specialized proteins recognize these chemical modifications and thereby define the functional state of chromatin (Bartke et al., 2010; Nikolov et al., 2011; Vermeulen et al., 2010). Several individual chromatin-binding factors have been analyzed in detail. Also, proteomics approaches have taken inventory of factors interacting with single chromatin modifications. However, the full set of factors specific to particular modified chromatin domains, such as for example eu-and heterochromatin, is not known yet. In this thesis, I report my findings from a systematic in vitro chromatin affinity purification approach in combination with quantitative mass spectrometry (Nikolov et al., 2011) that significantly expands the list of proteins regulated by heterochromatic modifications, both alone and in combination. The results provide a comprehensive catalogue of proteins specifically regulated in their chromatin binding by specific modification patterns. Moreover, the datasets highlight novel biological functions associated with individual modifications and reveal unpredicted functional relationships of the investigated chromatin modifications. The analysis of the interactomes of combinatorially modified chromatin identifies for the first time proteins whose binding properties to chromatin depend on the cooperative action of two modifications. The results provide novel insights into the communication between two chromatin modifications, namely positive and negative crosstalk. Furthermore, I introduce a new experimental workflow combining chromatin affinity purification and cross-linking mass spectrometry. This workflow maps physical protein-protein interactions sites of chromatin-bound proteins and provides first insights into the hierarchy of protein recruitment to chromatin. Overall, my findings demonstrate that by using a template that mimics the native form of chromatin, which is not accessible by the widely used reductionist approaches, chromatin modifications can be analyzed in multiple dimensions. In combination with the new methods established here, my work will help to improve our understanding of epigenetic regulation of chromatin-associated processes.de
dc.contributor.coRefereeStark, Holger Prof. Dr.
dc.contributor.thirdRefereeFischer, André Prof. Dr.
dc.contributor.thirdRefereeJohnsen, Steven Prof. Dr.
dc.contributor.thirdRefereeDoenecke, Detlef Prof. Dr.
dc.contributor.thirdRefereeUrlaub, Henning Prof. Dr.
dc.subject.engheterochromatinde
dc.subject.enghistone modification readoutde
dc.subject.enghistone modification crosstalkde
dc.subject.engchromatin affinity purificationde
dc.subject.engchromatin binding interactomede
dc.identifier.urnurn:nbn:de:gbv:7-11858/00-1735-0000-0023-3E76-7-2
dc.affiliation.instituteGöttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)de
dc.subject.gokfullBiologie (PPN619462639)de
dc.identifier.ppn890351546


Dateien

Thumbnail

Das Dokument erscheint in:

Zur Kurzanzeige