The role of H2B monoubiquitination in cellular differentiation

Karpiuk, Oleksandra

dc.contributor.advisor	Johnsen, Steven Prof. Dr.	de
dc.contributor.author	Karpiuk, Oleksandra	de
dc.date.accessioned	2013-06-24T10:35:31Z	de
dc.date.available	2013-06-24T10:35:31Z	de
dc.date.issued	2013-06-24	de
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0001-B957-4	de
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-3898
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc	570	de
dc.title	The role of H2B monoubiquitination in cellular differentiation	de
dc.type	doctoralThesis	de
dc.contributor.referee	Shcherbata, Halyna Dr.	de
dc.date.examination	2012-11-05	de
dc.description.abstracteng	Histones, subjected to post-translational modifications, are important regulators of the cellular processes. One of these modifications is monoubiquitination of histone H2B (H2Bub1). H2Bub1 is associated with the actively transcribed genes. Moreover, H2Bub1 is required for the proper DNA repair and was recently reported to be lost during tumor progression. The levels of H2Bub1 in the cell are tightly regulated. In mammals, ubiquitination is mediated by the E3 ubiquitin ligase RNF20/40. Another important upstream regulator of H2Bub1 is the CDK9 enzyme that promotes transcriptional elongation. It, together with an adaptor protein WAC, facilitates the RNF20/40 recruitment to the chromatin. Differentiation of the cell is a process that results in cellular specialization and acquiring a physiological function. It is accompanied by the significant changes in gene expression and in histone modification patterns. This project aimed to understand the role of H2Bub1 in cellular differentiation. Investigating human mesenchymal stem cells (hMSCs) it was observed that the H2Bub1 levels increase during differentiation into osteoblasts and adipocytes. Depletion of the H2Bub1 regulators RNF40, WAC and CDK9 resulted in inhibition of the hMSC differentiation suggesting that H2Bub1 is required for the correct progression of this process. Mechanistically, H2Bub1 was shown to participate in the activation of the “bivalent” genes that carry activatory and inhibitory histone marks. H2Bub1 deposition is required for removal of the repressive H3K27me3 from the differentiation-dependent genes. Taken together, these observations for the first time demonstrate the involvement of H2Bub1 in cellular differentiation. The proposed model suggests that H2Bub1 executes its function via promoting the resolution of bivalency on the differentiation-specific genes. These results give additional insights into H2Bub1 function during transcription of the certain subsets of genes. The obtained knowledge increases our understanding of the transcriptional regulation, carcinogenesis and stem cell biology.	de
dc.contributor.coReferee	Hahn, Heidi Prof. Dr.	de
dc.subject.eng	H2B monoubiquitination	de
dc.subject.eng	RNF20	de
dc.subject.eng	RNF40	de
dc.subject.eng	differentiation	de
dc.subject.eng	mesenchymal stem cells	de
dc.subject.eng	cyclin-dependent kinase 9	de
dc.subject.eng	histone modifications	de
dc.subject.eng	epigenetics	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-0001-B957-4-3	de
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)	de
dc.subject.gokfull	Biologie (PPN619462639)	de
dc.identifier.ppn	750586311	de

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GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1115]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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