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Appearance of Chromatin Depends on Salt Concentration

Appearance of Chromatin Depends on Salt Concentration. Chromatin consists of DNA complexed with proteins. 30 nm fiber. Beads on a string. from Lodish et al ., Molecular Cell Biology, 6 th ed. Fig 6-28. Chromatin Organization and Folding.

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Appearance of Chromatin Depends on Salt Concentration

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  1. Appearance of Chromatin Depends on Salt Concentration Chromatin consists of DNA complexed with proteins 30 nm fiber Beads on a string from Lodish et al., Molecular Cell Biology, 6th ed. Fig 6-28

  2. Chromatin Organization and Folding From Fyodorov et al., Nature Rev.Mol.Cell Biol. 19, 192 (2018) The nucleosome core particle contains 147 bp of DNA wrapped around an octamer of core histones H1 associates with the nucleosome core particle to form the chromatosome core particle Internucleosomal interactions compact chromatin further

  3. Nucleosome Structure Nucleosomes contain 2 copies of H2A, H2B, H3 and H4 147 bp of DNA is wrapped around nucleosome Histone tails emanate from core Some nucleosomes contain histone variants H1 is a linker histone and facilitates chromatin compaction from Jiang and Pugh, Nature Rev.Genet. 10, 161 (2009)

  4. Chromatin Structure is Dynamic Cellular chromatin consists of liquid-like, irregularly-folded 10 nM fibers from Maeshima et al., Curr.Opin.Genet.Dev. 37, 36 (2016)

  5. Cohesin and Condensin Shape Chromatin Architecture Cohesin and condensin contain a SMC heterodimer and non-SMC regulatory subunits The head region of the SMC proteins are ATP-binding domains The ATPase cycle leads to entrapment of DNA from Hagstrom and Meyer, Nature Rev.Genet. 4, 520 (2003)

  6. Mechanism of DNA Entrapment by Cohesin from Hirano, Cell164, 847 (2016) ATP binding induces head-head engagement ATP hydrolysis triggers disengagement, opening the ring structure Closing the ring leads to entrapment

  7. Formation of Chromatin Loops CTCF is best known as a protein that restricts enhancer-promoter interactions CTCF binds DNA and recruits cohesin Cohesin is a loop extrusion motor and forms chromatin loops defined by CTCF Loops bring enhancers in proximity with target promoters from Bonev and Cavalli, Nature Rev.Genet.17, 661 (2016)

  8. Chromosome Conformation Capture from Bonev and Cavalli, Nature Rev.Genet.17, 661 (2016) 3C methods interaction frequencies between genome loci Hi-C is an unbiased, genome-wide method in which the crosslinked genome is digested, biotinylated, and ligated Interaction products are purified and analyzed by sequencing

  9. A Simulated Hi-C Map Shows TADs Represented as Triangles The color scale corresponds to contact frequency TAD and loop boundaries are bound by CTCF and cohesin from Hansen et al., Nucleus 9, 20 (2018)

  10. Topologically-Associating Domains Irregularly-folded 10 nm fibers form TADs TADs interact with each other more than the rest of the ganome TADs form a fundamental layer of chromosome folding TAD boundaries are enriched in CTCF TAD structure can fluctuate as a result of liquid-like movement of chromatin TADs are associated with common epigenetic features from Maeshima et al., Curr.Opin.Genet.Dev. 37, 36 (2016)

  11. Large TADs are Divided into subTADs Most CTCF binding sites are within TADs Loops within a TAD bring distant genomic regions into proximity from Bonev and Cavalli, Nature Rev.Genet.17, 661 (2016)

  12. Consequences of Deletion of a Boundary Element from Bonev and Cavalli, Nature Rev.Genet.17, 661 (2016) Deletion of a boundary element can cause changes in gene expression Novel loops can lead to misexpression of important genes

  13. Structural Organization of Chromatin from Hansen et al., Nucleus 9, 20 (2018) Chromatin is organized into TADs Interaction between TADs of the same epigenetic type give rise to compartments A compartments are active and localize near nuclear speckles B compartments are inactive and localize near the nuclear envelope Chromosome territories are formed by coalescence of compartments

  14. TADs Switch Between Compartments from Bonev and Cavalli, Nature Rev.Genet.17, 661 (2016) TADs and loops are dynamic TAD switching occurs in a cell type-specific manner

  15. Circadian Oscillation of Chromatin Folding TADs increase enhancer- promoter contacts Circadian changes in sub-TADs within stable TADs Clock genes activated the expression of Rev-erba, which functions as a repressor of clock genes Rev-erba is involved in the eviction of factors involved in loop formation to form sub-TADs from Mallet de Lima and Gondor, Science359, 1212 (2018)

  16. Levels of Chromatin Folding in the Nucleus Nucleosomes Nucleosomes 30 nm fibers Chromatin fibers Higher order structure Chromosome domains (TADs) Compartments Chromosome territories

  17. Dynamic Interactions of Condensins Fold and Compact Nucleosomes from Hirano, Cell164, 847 (2016) Condensins contain a SMC heterodimer and entrap DNA by ATP hydrolysis Chromatin structure changes throughout the cell cycle and confers rigidity to chromosome arms

  18. Nucleosome Structure Nucleosomes contain 2 copies of H2A, H2B, H3 and H4 147 bp of DNA is wrapped around nucleosome Histone tails emanate from core Some nucleosomes contain histone variants H1 is a linker histone and facilitates chromatin compaction from Jiang and Pugh, Nature Rev.Genet. 10, 161 (2009)

  19. Nucleosomal Histones and Their Variants from Sarma and Reinberg, Nature Rev.Mol.Cell Biol.6, 139 (2005)

  20. Histone Exchange From Venkatesh and Workman, Nature Rev.Mol.Cell Biol.16, 178 (2015) Incorporation of histone variants is replication-independent Chromatin remodellers and histone chaperones mediate histone exchange Chromatin modifications facilitate histone exchange H2A.Z-containing nucleosomes are less stable and facilitates nucleosome depletion

  21. Expression of Testis-Specific Histone Variants During Spermatogenesis from Hoghoughi et al., J. Biochem. 163, 97 (2018) Histone replacement by protamines are essential for production of male gametes Histone variants are expressed in a temporal barrier In round spermatids, H2A.B.3 is associated with X-linked genes that escape X-inactivation Protamines are removed after fertilization, and are replaced by somatic histones in early development

  22. The Process of Histone to Protamine Replacement H2A.L.2 creates an open structure to enable loading of TPs TPs drives the recruitment and processing of protamines from Hoghoughi et al., J. Biochem. 163, 97 (2018)

  23. Protamines are Related to H1 Histone replacement by protamines are essential for production of male gametes A spermatid-specific histone variant (H2A.L.2) is loaded onto nucleosomes H2A.L.2 enables loading of transition proteins that recruit and process protamines from Eirin-Lopez and Ausio, BioEssays31, 1062 (2009)

  24. Regulation of DNA Accessibility from Jiang and Pugh, Nature Rev.Genet. 10, 161 (2009) Nucleosome sliding exposes binding sites Chromatin remodelling complexes extract DNA from the nucleosome surface Nucleosome eviction may be necessary for transcription initiation Histone chaperones incorporate or evict histone variants

  25. Assembly of Nucleosomes Histone chaperones assemble histones into nucleosomes and prevent non- specific associations of histones with DNA The central region of nucleosomal DNA is first organized by H3/H4 heterotetramer H2A-H2B heterotetramer is subsequently loaded onto the nucleosome from Das et al., Trends Biochem.Sci. 35, 476 (2010)

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