Chromatin Regulation September 20, 2017

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

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

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

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)

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

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

Nucleosome Breathing

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

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 http://faculty.jsd.claremont.edu/jarmstrong/researchint.htm

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

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

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

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!

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

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

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

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

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

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!