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Chromatin remodeling
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- 2. Contents: 1. Chromatin Remodeling 2.Chromatin Remodeling Complexes 3. Mechanisms of Chromatin Remodeling 4. Disorders of Chromatin Remodeling 5. Chromatin Immunoprecipitation Sequencing
- 3. ATP-dependent chromatinremodeling, 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 ofthe events of gene expression
- 5. Structural backbone or A molecularspool for DNA Gene Expression Replication, DNA repair Recombination Histones
- 6. Chromatin Remodeling ComplexesAlter 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.
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- 8. A summary ofthe different classes of nucleosome remodeling ATPases and reactions they catalyze.
- 9. 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
- 10. Target location signalsand translocation reaction scheme for chromatin remodelers.
- 11. One •Nucleosome Sliding Two •eject histoneoctamers Three •Remove H2A-H2B dimers Four •replace dimers Mechanisms of Chromatin Remodeling
- 12. Mechanisms of ChromatinRemodeling
- 13. Start SWI/SNF ATPase 4 ATP hydrolysis displaces the nucleosom rebind forms alarger DNA bulge DNA rewrapped end 1. Nucleosome Sliding
- 14. ATP-dependent chromatin remodeling. (a)change the locations of nucleosomes
- 15. 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.
- 16. 2. Nucleosome ejection Allmembers of the SWI/SNF family and only a subset of ISWI remodelers are able to eject histone dimers. 1. DNA loops Remove dimers or the entire octamer 2. Tendency of the octamer to dissociate into H2A–H2B dimers and the (H3–H4)2 tetramer 3. Large loops may allow for other DNA molecules to invade the open histone-DNA contacts 4. DNA translocation release of the neighboring histone dimer or octamer
- 17. ATP-dependent chromatin remodeling. (b)remove histones from the DNA
- 18. Proposed Mechanism ofSWI/SNF Nucleosome Eviction
- 19. Histone Exchange TheSWR1 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
- 20. ATP-dependent chromatin remodeling. (c)replace core histones with variant histones.
- 21. Role of histonetails 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.
- 22. Histone modifications andtheir effects on nucleosome structure
- 23. Histone modifications andtheir effects on nucleosome structure
- 24. Acetylated histones allow transcriptionto begin. Once acetyl groups are added to particular amino acids in the tails of certain histones, the TATA box becomes accessible to transcription factors.
- 25. Reactions catalyzed byATP-dependent chromatin remodeling factors
- 28. Disorders of ChromatinRemodeling
- 29. Chromatin Evaluation Techniques DNase footprinting assay enzymaticassaysModel systems Nucleosomal arrays Electromobility gel shift assay (EMSA) Chromatin Immunoprecipitation (ChIP)
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- 34. Eukaryotic Genes AreFlanked by Nucleosome-Free Regions and Well-Positioned Nucleosomes
- 35. Transcriptional Activation InvolvesChanges in Nucleosome Locations, Composition, and Histone Modifications