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

2. Nuclear organization Nucleolus Cajal bodies speckles

3. Common translocations Chromatin domains

5. H3 H4 H2A H2B

6. Histone modifications

7. DNA Methylation at CpG sites

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

18. Nucleosome positioning and gene structure

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

24. Eukaryotic pre-mRNA expression

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

34. SR proteins are trans-acting splicing factors

39. Trans-splicing (C. elegans)

41. RNA editing

43. Eukaryotic mRNA degradation

45. Nonsense-meditaed mRNA decay

46. Alternative splicing and NMD to control gene expression