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BME 130 – Genomes Lecture 14 Chromatin, Gene expression, and splicing.

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Presentation on theme: "BME 130 – Genomes Lecture 14 Chromatin, Gene expression, and splicing."— Presentation transcript:

1 BME 130 – Genomes Lecture 14 Chromatin, Gene expression, and splicing

2 Nuclear organization Nucleolus Cajal bodies speckles

3 Common translocations Chromatin domains

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5 H3 H4 H2A H2B

6 Histone modifications

7 DNA Methylation at CpG sites

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9 CHiP-Seq DNA DNA-binding proteins (histones, e.g) crosslink Immuno-precipitate and fragment DNA Immuno-precipitate and fragment DNA Reverse cross-links and sequence

10 ChIP-Seq and ChIP-chip comparison of two histone marks Lower background & tighter peaks in ChIP-Seq (better contrast) trxG (activation) PcG (repression)

11 Highly dynamic histone modification during differentiation Neural txn factor House- keeping Neuro- genesis txn factor adipose txn factor Neural progenitor marker Brain & lung txn factor

12 Promoter classes high CpG gene low CpG intermediate CpG CpG Highly expressed, housekeeping genes; other genes N=11,410 Genes with high tissue-specificity N=3,014 Mixture of genes N=3,338

13 NPC=neural progenitor cellsMEF=embryonic fibroblastsES = embryonic stem cells

14 H3K36me3 marks gene bodies (may prevent aberrant transcriptional initiation)

15 Imprinting is reflected in H3K36me3 state

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18 Nucleosome positioning and gene structure

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23 Histone modification in cell division Haspin H3 P P Survivin Chromosomal passenger complex AuroraB (kinase)

24 Eukaryotic pre-mRNA expression

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26 Eukaryotic RNAPol II transcripts have a 7-methyl-G cap

27 Eukaryotic 3’ end processing

28 Splicing

29 Intron flavors

30 Intron content varies widely

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34 SR proteins are trans-acting splicing factors

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39 Trans-splicing (C. elegans)

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41 RNA editing

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43 Eukaryotic mRNA degradation

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45 Nonsense-meditaed mRNA decay

46 Alternative splicing and NMD to control gene expression

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