Chromatin remodeling

chromatin remodeling 2012

1. CHROMATIN REMODELING Maryam Amini Winter 2012

2. Contents: Chromatin Remodeling Chromatin Remodeling Complexes Mechanisms of Chromatin Remodeling Disorders of Chromatin Remodeling Chromatin Immunoprecipitation Sequencing

3. ATP-dependent chromatin remodeling, or simply chromatin remodeling , refers to dynamic changes in the structure of chromatin that occur during the life of a cell. Introduction

4. A summary of the events of gene expression

5. Chromatin Remodeling Complexes Alter the Positions and Compositions of Nucleosomes A key role of some transcriptional activators is to orchestrate changes in chromatin structure from the closed to the open conformation by altering Nucleosomes. One way to change chromatin structure is through ATP dependent chromatin remodeling. All remodeling complexes have a catalytic ATPase subunit that is similar to other motor proteins, called DNA translocases , that move along the DNA.

6. A summary of the different classes of nucleosome remodeling ATPases and reactions they catalyze.

7. main families: → SWI/SNF: enzyme contains bromo -domain that binds to acetylated histone → CHD: enzyme contains chromo-domain that binds to methylated histone ATP-dependent chromatin remodeling complexes

8. Target location signals and translocation reaction scheme for chromatin remodelers.

9. Mechanisms of Chromatin Remodeling

10. Mechanisms of Chromatin Remodeling

11. 1. Nucleosome Sliding

12. ATP-dependent chromatin remodeling. (a) change the locations of nucleosomes

13. Nucleosome Conformational Change Sliding provides an efficient way to allow access to DNA which was once contained within a nucleosome. The SWI/SNF complex create accessible DNA by generating stable DNA loops within the context of the nucleosome. The average loop size on nucleosomal templates approximately 100 bp.

14. 2. Nucleosome ejection All members of the SWI/SNF family and only a subset of ISWI remodelers are able to eject histone dimers. DNA loops Remove dimers or the entire octamer Tendency of the octamer to dissociate into H2A–H2B dimers and the (H3–H4)2 tetramer Large loops may allow for other DNA molecules to invade the open histone-DNA contacts DNA translocation release of the neighboring histone dimer or octamer

15. ATP-dependent chromatin remodeling. (b) remove histones from the DNA

16. Proposed Mechanism of SWI/SNF Nucleosome Eviction

17. Histone Exchange The SWR1 complex catalyzes the exchange of nucleosomal H2A for the H2AZ variant . relaxation of DNA Release of H2AZ-H2B from the SWR1 complex reassembly of a histone octamer containing one of each H2AZ–H2B and H2A–H2B

18. ATP-dependent chromatin remodeling. (c) replace core histones with variant histones.

19. Role of histone tails Histone tails have been found to be required for the nucleosome remodeling activity of some remodeler complexes and not for others . Modification of histone tails can affect remodeler complex recruitment and stability . Histone acetylation stabilizes SWI/SNF interaction with nucleosomes.

20. Histone modifications and their effects on nucleosome structure

21. Histone modifications and their effects on nucleosome structure

22. Acetylated histones allow transcription to begin . Once acetyl groups are added to particular amino acids in the tails of certain histones, the TATA box becomes accessible to transcription factors.

23. Reactions catalyzed by ATP-dependent chromatin remodeling factors

24. Disorders of Chromatin Remodeling

25. Nucleosomal arrays Electromobility gel shift assay (EMSA ) Chromatin Immunoprecipitation ( ChIP )

26. Chromatin immunoprecipitation ( ChIP )

27. Eukaryotic Genes Are Flanked by Nucleosome-Free Regions and Well-Positioned Nucleosomes

28. Transcriptional Activation Involves Changes in Nucleosome Locations, Composition, and Histone Modifications

29. Thanks for your attention