Zeitplan 2008 Teil Renkawitz-Pohl Di 22. 01.: 1 Genregulation in Eukaryoten (Einführung) Steroidhormone und Genregulation Mi 23. 01.: 2 Chromatinreorganisation in der Spermatogenese und Translationskontrolle Eisenstoffwechsel und Translationslkontolle Do 24. 01.: fällt aus! Fr 25. 01.: 3. Sex determination Säugetiere (...der kleine Unterschied...) (Transkription, Hormone, Signalketten) 4. Sexdetermination Drosophila (Differentielles Splicing) Fragebögen verteilen Di 29. 01.: 5 Dosiskompensation Drosophila (Regulation auf Chromatin-Ebene) Dosiskompensation Säugetiere (Regulation auf Chromatin-Ebene) Mi 30. 01.: 6 Zelladhäsion und Kommunikation Fragebögen verteilen
Transcript
Zeitplan 2008 Teil Renkawitz-Pohl
Di 22. 01.: 1 Genregulation in Eukaryoten (Einführung)Steroidhormone und Genregulation
Mi 23. 01.: 2 Chromatinreorganisation in der Spermatogenese
und TranslationskontrolleEisenstoffwechsel und Translationslkontolle
Do 24. 01.: fällt aus!
Fr 25. 01.: 3. Sex determination Säugetiere (...der kleine Unterschied...)
Di 29. 01.: 5 Dosiskompensation Drosophila (Regulation auf Chromatin-Ebene)
Dosiskompensation Säugetiere (Regulation auf Chromatin-Ebene)
Mi 30. 01.: 6 Zelladhäsion und Kommunikation Fragebögen verteilen
Do 31.01.: 7 Signalketten in Entwicklung und Tumorentstehung
Fr 01. 02.: 8 Fragen zur Woche/ Fragebögen besprechenKlausurvorbereitung
Genregulation in Eukaryoten
1) Regulation der Transkription2) Posttranskriptionelle Regulation• Differentielles Splicing(siehe Geschlechtbestimmung)• Kontrolle der Translation (siehe Spermatogenese als Beispiel)• Proteinmodifikationen (siehe Teil Prof. Lingelbach)
Eukaryoten:Kontrollmöglichkeiten
aus Alberts: 9-2
erst auf Chromatinebene, dann:
CappingPolyadenylationSplicing
Chromatinstruktur
Chromatin: wie passt das gesamte Genom in die
Zelle?
Zur Anzeige wird der QuickTime™ Dekompressor “Animation”
benötigt.
Figure 9-35. Model for the packing of chromatin and the chromosome scaffold in metaphase chromosomes. In interphase chromosomes, long stretches of 30-nm chromatin loop out from extended scaffolds. In metaphase chromosomes, the scaffold is folded into a helix and further packed into a highly compacted structure, whose precise geometry has not been determined.
Figure 9-30. Structure of the nucleosome. (a) Ribbon diagram of the nucleosome shown face-on (left) and from the side (right). One DNA strand is shown in green and the other in brown. H2A is yellow; H2B, red; H3, blue; H4, green. (b) Space-filling model shown from the side. DNA is shown in white; histones are colored as in (a). H2A, H2A', H2B, H2B', H3, and H4 indicate the positions of the respective histone N-terminal tails visible in this view. The H2A' N-terminal tail interacts with the upper loop of DNA, while the H2A N-terminal tail (only partially seen in this view) interacts with the bottom loop of DNA. The N-terminal tail of one H4 extends from the bottom of the nucleosome and interacts with the neighboring histone octamer in the crystal lattice (not shown). The N-terminal tails of histones H2B, H2B', H3, and H3' pass between the two loops of DNA. The N-terminal tails of H2A, H4, H3, and H2B include an additional 3, 15, 19, and 23 residues, respectively, that are not visualized in the crystal structure because they are not highly structured. They extend further from the surface of the nucleosome where they may participate in nucleosome-nucleosome interactions in the 30 nm fiber (See Figure 9-31) or interact with other chromatin-associated proteins. [From K. Luger et al., 1997, Nature 389:251; courtesy of T. J. Richmond.]
Figure 9-31. Solenoid model of the 30-nm condensed chromatin fiber in a side view. The octameric histone core (see Figure 9-30) is shown as an orange disk. Each nucleosome associates with one H1 molecule, and the fiber coils into a solenoid structure with a diameter of 30 nm. [Adapted from M. Grunstein, 1992, Sci. Am. 267:68]
dazu würde es geringere Affinität zwischen den basischen Histonenund der DNA bedürfen!
Aus: Alberts et al.:
Molecular Biology of the Cell. Fourth Edition, 2002.
Fig. 7-45
Histonacetylase und Chromatinöffnung
Aus:
Alberts et al.: Molecular Biology of the Cell. Fourth Edition, 2002.
Fig. 7-46
HAT Wirkung
Aus:
Alberts et al.: Molecular Biology of the Cell. Fourth Edition, 2002.
Fig. 7-49
HDATHiston-
Deacetylasen
führen zu
inaktivem Chromatin
Genregulation in Eukaryoten
1) Regulation der Transkription2) Posttranskriptionelle Regulation• Differentielles Splicing• Kontrolle der Translation• Proteinmodifikationen
pre-mRNA, RNP, mRNA
Prokaryoten: in der Regel kolinear:
Gen - mRNA
aus:Alberts et al.Fig. 6-1
Eukaryoten
Genregulation in Eukaryoten
1) Regulation der Transkription2) Posttranskriptionelle Regulation• Differentielles Splicing(Beispiel: Sex determination Drosophila)• Heute: Splicing im Prinzip)• Kontrolle der Translation• Proteinmodifikationen
Eukaryoten:premRNA-reife mRNA
SplicingGen und mRNA sind nicht
kolinear
aus:Alberts etal.Fig.8-50 Technik: R-loop Analyse im EM
Introns und Exons
aus:AlbertsFigure 8-7
Biologischer Sinn
exon shuffling: Evolution
differentielles Splicing: 1 Gen mehrere Proteine
Splisosomen an der naszierenden premRNA
EM
Schema aus:AlbertsFigure 8-52
Splice-Erkennungssequenzen
aus Alberts, Fig. 8-53
Splicing Mechanismus(Introns: 100 bp bis mehrere kbp
z.B. 40 kbp)
aus AlbertsFig. 8-84
Details inFM GENETIK
Was müßte man machen, um Splicing zu
verhindern für Exon-Skipping?
Splice site durch RNA oder Protein maskieren!
5´und 3´Modifikationender eukaryotischen
mRNAa) 5´Cappingb) 3´Polyadenylation
Figure 4-19. Overview of RNA processing in eukaryotes using -globin gene as an example. The -globin gene contains three protein-coding exons (red) and two intervening noncoding introns (blue). The introns interrupt the protein-coding sequence between the codons for amino acids 31 and 32 and 105 and 106. Transcription of this and many other genes starts slightly upstream of the 5' exon and extends downstream of the 3' exon, resulting in noncoding regions (gray) at the ends of the primary transcript. These regions, referred to as untranslated regions (UTRs), are retained during processing. The 5' 7-methylguanylate cap (m7Gppp; green dot) is added during formation of the primary RNA transcript, which extends beyond the poly(A) site. After cleavage at the poly(A) site and addition of multiple A residues to the 3' end, splicing removes the introns and joins the exons. The small numbers refer to positions in the 147-aa sequence of -globin.Aus: Molecular Cell Biology, 4. Edition, Lodish et. al.
Primärtranskript-mRNA
Differentielles SplicingBeispiel:
Synthese eines membranständigen und eines sekretierten Antikörpers(siehe Kernmodul 3)
Beispiel: Geschlechtsbestimmung bei Drosophila (dieses Fachmodul)
