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Nuclear Organization
Interaktionen von RNAs und Proteinen
Sonja Prohaska
Computational EvoDevo groupUniversität Leipzig
SS2019
Interaktionen von RNAs und Proteinen
Nuclear Organization
DNA-DNA Interactions: Nuclear Organization
Interaktionen von RNAs und Proteinen
Nuclear Organization
Nuclear Bodies Associated and Their Function
Interaktionen von RNAs und Proteinen
Nuclear Organization
Organization of Nuclear Bodies by Long Noncoding RNAsarcRNAs: architectural long noncoding RNAs
I nascent arcRNAs serve as scaffold for RNA binding proteinsI results in strong local enrichment of specific factors
Interaktionen von RNAs und Proteinen
Nuclear Organization
Chromosome Terretories
Interaktionen von RNAs und Proteinen
Nuclear Organization
Attachment of Chromatin to Nuclear Envelope
I S/MARs: Scaffold/Membane attachment regions
Interaktionen von RNAs und Proteinen
Nuclear Organization
A Special Terretory: Ihe Inactive X Chromosome
Dosage compensition in placental mammalsWHAT is happening?
I random X-inactivation
I female: X, X → Xa (active), Xi (inactive)I male: X, Y → Xa
Interaktionen von RNAs und Proteinen
Nuclear Organization
X Chromosome Inactivation (XCI)HOW is it happening?
Interaktionen von RNAs und Proteinen
Nuclear Organization
XCI – Counting and Choosing
serveral model try to explainInteraktionen von RNAs und Proteinen
Nuclear Organization
XCI – Main Player(s) Xist (and Tsix)
I lncRNA Xist (X-inactive specific transcript)expressed from inactive X chromosomeis responsible for silencing the X in cis → Xi (inactive)
I lncRNA Tsix (antisense of Xist)expressed from active X chromosomeis responsible for silencing Xist in cis → Xa (active)
Interaktionen von RNAs und Proteinen
Nuclear Organization
The X Inactivation Center (Xic)
I Xist: X-inactivation specific transcript17kb, spliced and polyadenylated transcript
I Tsix: antisense RNA of Xist
I genes (RNA or protein coding) promoting Xist expression
I genes (RNA or protein coding) supressing Xist expression
Interaktionen von RNAs und Proteinen
Nuclear Organization
Proposed mechanisms
I Xist has binding sites for proteins (similar to arcRNAs)
I SPEN binds “repeatA” on Xistinteracts with SMRT-HDAC3 → deacetylationmay recruit PRC2 → H3K27me3 (repressive mark)may recruit PRC1 → H2AK119ub (repressive mark)excludes PolII from Xist-coated chromosome
I RBM15-WTAP interacts with Xistrecruits m6A mashiney that methylates XistYTHDC1 reads m6A enables transcriptional scilencing
I LBR (lamina binding receptor) links Xist-coated chromatin tolamin in the lamina
Interaktionen von RNAs und Proteinen
Nuclear Organization
Xist Spreading and Lamina Localization
Interaktionen von RNAs und Proteinen
Nuclear Organization
TADs at the Xic
Interaktionen von RNAs und Proteinen
Nuclear Organization
Measuring Chromatin Interactions
Chromosome Conformation Capture
I a method to measure chromatin-chromatin interactions
Hi-C Method
Interaktionen von RNAs und Proteinen
Nuclear Organization
Topologically Associated Domains (TADs)Structure of TADs
Interaktionen von RNAs und Proteinen
Nuclear Organization
Topologically Associated Domains (TADs)Functional/Regulatory Relevance
Interaktionen von RNAs und Proteinen
Nuclear Organization
ReferencesI van Bemmel et al.
The bipartite TAD organization of the X-inactivation center ensures opposingdevelopmental regulation of Tsix and XistNature Genetics 51, 1024–1034 (2019)
I Cerase et al.Phase separation drives X-chromosome inactivation: a hypothesisNature Structural and Molecular Biology 26, 331–334 (2019)
I Chen et al.Xist recruits the X chromosome to the nuclear lamina to enablechromosome-wide silencingScience 6311(354), 468–472 (2016)
I Wang et al.Comment on “Xist recruits the X chromosome to the nuclear lamina to enablechromosome-wide silencing”Science 6343(356), eaal4976 (2017)
I Pollex et al.Nuclear positioning and pairing of X-chromosome inactivation centers are notprimary determinants during initiation of random X-inactivationNature genetics 51.2 (2019): 285.
I da Rocha et al.Novel players in X inactivation: insights into Xist-mediated gene silencing andchromosome conformationNature Structural and Molecular Biology volume 24, pages 197–204 (2017)
Interaktionen von RNAs und Proteinen
Nuclear Organization
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