1. Chromatin Regulation
September 20, 2017

2. Nucleosome position is dynamic
The positions of nucleosomes on the chromosome often change according to:
Changes in the cell cycle
2. Transcriptional activity

3. Nucleosome-DNA interactions are dynamic
Cell Cycle: The forms of chromatin change during the cell cycle, becoming most condensed at mitosis

4. The Cell Cycle Mitosis: DNA is more compact Interphase:
DNA is less compact
The Cell Cycle
Figure 8-17
Nucleosome assembly link 4

5. Nucleosome Positioning is Dynamic
Transcriptional Regulation
Regions of the DNA are associated with many nucleosomes have lower rates of transcription (Heterochromatin)
It is important that some regions of the DNA have sparsely placed nucleosomes so that DNA regulatory proteins can bind to the DNA (Euchromatin)

8. Nucleosome Positioning
How is nucleosome positioning regulated?
1. DNA Sequence
2. DNA Breathing
3. Nucleosome Sliding
4. Nucleosome Positioning
5. Chromatin Remodeling

9. DNA Sequence
A:T rich areas of DNA can bend more easily around the histone

10. Nucleosome Breathing

12. Nucleosome Positioning
Negative and Position Regulation
Negative Regulation
Positive Regulation
Nucleosome binding protein

13. Chromatin Remodeling Complexes
Large multiprotein complexes that facilitate changes in nucleosome location or interactions with DNA using ATP hydrolysis for energy. Recognize modified histones tail with a Bromo- or Chromodomain.
Common names:
Swi/Snf complex
NURF complex

14. Chromatin Remodeling Complexes
-Can Expose DNA Binding Sites for Transcriptional Control
Picture from Genetics: Analysis of Genes and Genomes, 6th Edition

15. Histone Modifications
Histone Tails are HIGHLY modified post-translationally with small molecules
Patterns of histone modifications regulate
Active promoter regions
Active transcribed genes
Repressed genes
Stem cells
Chromosome condensation

16. Histone Modifications
How are histone tails modified?
P=Phosphorylation
Me: Methylation
Ac=Acetylation
Ub: Ubiquitinylation

17. Histone Code Hypothesis
Modifications on histones affect activation and repression of genes
Understanding the different variations of histone modifications may “open up” a novel understanding of regulation
Some of these modifications can be maintained during cell division or inherited.
Histone modification are part of epigenetic regulation
Circle the one we will talk about in the paper!

19. Histone Modifications
What do these modifications do?
Weaken the association of the nucleosome with DNA
Inhibit the higher order nucleosome assembly
Recruit specific proteins to the chromatin
Some proteins can recognize the modified histone tails

20. Histone Modifications
Acetyl groups carries a negative charge.
Acetylation of lysine cancels the positive charge
Histone tails are more weakly associated with the nucleosomes– thus cannot form higher order assemblies (ie. 30 nm fiber)
Tends to decreases packing
Methyl groups are neutral.
Histone tails maintain association with the nucleosomes.
Tends to increase packing

21. Histone Modifications
Histone modifications create
domains for histone modifying proteins to bind.

22. Histone Modifications
Changes the affinity of histones to the DNA
Creates binding sites for other proteins to bind

23. Histone Modifications
What modifies histones?
Histone Acetyltransferases
Histone Deacetylatse complexes
Histone Methyltransferases
Histone Demethylases

34. Histone Modifications
How are modifications of histones passed on during DNA replication?
How is the “memory” of histone modifications maintained?
Circle the one we will talk about in the paper!