Interaktionen von RNAs und Proteinen - uni-leipzig.de · 2019. 6. 7. · Interaktionen von RNAs und...
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Nuclear Organization
Interaktionen von RNAs und Proteinen
Sonja Prohaska
Computational EvoDevo groupUniversität Leipzig
SS2019
Interaktionen von RNAs und Proteinen
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DNA-DNA Interactions: Nuclear Organization
Interaktionen von RNAs und Proteinen
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Nuclear Bodies Associated and Their Function
Interaktionen von RNAs und Proteinen
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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
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Chromosome Terretories
Interaktionen von RNAs und Proteinen
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Attachment of Chromatin to Nuclear Envelope
I S/MARs: Scaffold/Membane attachment regions
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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
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X Chromosome Inactivation (XCI)HOW is it happening?
Interaktionen von RNAs und Proteinen
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XCI – Counting and Choosing
serveral model try to explainInteraktionen von RNAs und Proteinen
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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
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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
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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
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Xist Spreading and Lamina Localization
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TADs at the Xic
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Measuring Chromatin Interactions
Chromosome Conformation Capture
I a method to measure chromatin-chromatin interactions
Hi-C Method
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Topologically Associated Domains (TADs)Structure of TADs
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Topologically Associated Domains (TADs)Functional/Regulatory Relevance
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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