DNA Packaging & Chromatin Architecture PDF
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Uploaded by GodlikeSerenity2747
Universiti Malaya
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Summary
This document provides a detailed overview of DNA packaging and chromatin architecture. It explains the structures and interactions that tightly pack DNA within the nucleus. The document includes diagrams to illustrate the various levels of organization, from the nucleosome to higher-order structures like the 30nm fiber.
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12/17/24 DNA packaging & chromatin architecture 1. Nucleosome structure and chromatin 2. Histone Octamer 3. Histone fold 4. Euchromatin and heterochromatin 1 12/17/24 The Chromos...
12/17/24 DNA packaging & chromatin architecture 1. Nucleosome structure and chromatin 2. Histone Octamer 3. Histone fold 4. Euchromatin and heterochromatin 1 12/17/24 The Chromosome 2 12/17/24 Chromosome and Histone proteins The word chromosomes is derived from the Greek word Chroma= colour and body= soma. The material that is made up of chromosome is referred to as chromatin. The fundamental unit of chromatin is the Nucleosome core particle (NCP). The NCP is organised to 147bp of DNA in 1.7 left handed super helical turn around and octamer of 4 core histones. The histones are H2A, H2B, H3 and H4. Small section of the DNA call the DNA linker serve to join the nucleosomes together and it is associated to with linker histone H1. Nucleosome core particle The octamer is first a tripartite arrangement with a H2A-H2B dimer flanked to a centrally located H3-H4 tetramer. 3 12/17/24 The “Octamer” Nucleosome core particle 4 12/17/24 Histone fold Common structural motif in histones are conserved among species which is known as histone fold. The histone motif is associated with the dimerization of the histone during the octamer formation. Histone fold consist of long central helix connected to two helix-strand-helix (HSH) motifs at opposite. Histone-histone interaction 5 12/17/24 Histone- DNA docking In the 147bp, 12 minor grooves out of 14 are facing towards the histone octamer. The interacAon of histone-‐DNA extends about 121bp. PosiAvely charged regions located in the N-‐terminal histone tails and nucleosome core will interact with the negaAvely charged phosphate backbone. Histone Chaperones Xenopus laevis egg extracts and histone-DNA mixture in vivo and in vitro assay This led to the isolation of nucleoplasmin as the first histone chaperones. Histone chaperones are group of acidic proteins that bind histones and participate in chromatin assembly and disassembly during transcription and replication of DNA. 6 12/17/24 Chromatin assembly and disassembly 7 12/17/24 Chromatin architecture One-start helix and two-start helix models- 30nm chromatin fibre. These two models for the 30nm chromatin fibre differ in topology, dimension and nucleosome packing density. One-start helix model: nucleosomes are adjacent to one another, packing density of 11 nucleosomes. Two-start helix model: zigzag arrangement of nucleosomes that stack on top of one another with packing density of 5 to 6 nucleosome. The need of linker DNA Other DNA binding proteins 8 12/17/24 Heterochromatin & Euchromatin The need for different compaction of DNA? Google list- Giemsa or quinacrine staining Heterochromatin The area of the chromosomes which are intensely stained with DNA-specific strains and are relatively condensed is known as heterochromatin. They are tightly packed form of DNA in the nucleus. The organization of heterochromatin is so highly compact in the way that these are inaccessible to the proteins engaged in gene expression. Even the chromosomal crossing over is not possible due to the above reason. Resulting them to be transcriptionally as well as genetically inactive. 9 12/17/24 Heterochromatin Heterochromatin is of two types: Facultative heterochromatin and constitutive heterochromatin. The genes which get silenced through the process of Histone methylation or siRNA or through RNAi are called as facultative heterochromatin. Hence they contain inactive genes and is not a permanent character of every nucleus of the cells. While the repetitive and structurally functional genes like telomeres or centromeres are called as Constitutive heterochromatin. These are the continuing nature of the cell’s nucleus and contains no gene in the genome. This structure is retainable during the interphase of the cell. The main function of the heterochromatin is to protect the DNA from the endonuclease damage; it is due to its compact nature. It also prevents the DNA regions to get accessed to proteins during gene expression Euchromatin That part of chromosomes, which are rich in gene concentrations and are loosely packed form of chromatin is called as euchromatin. They are active during transcription. Euchromatin covers the maximum part of the dynamic genome to the inner of the nucleus and is said that euchromatin contains about 90% of the entire human genome. To allow the transcription, some parts of the genome containing active genes are loosely packed. The wrapping of DNA is so loose that DNA can become readily available. The structure of euchromatin resembles the nucleosomes, which consist of histones proteins having around 147 base pairs of DNA wrapped around them. 10 12/17/24 Euchromatin Euchromatin actively participates in transcription from DNA to RNA. The gene regulating mechanism is the process of transforming euchromatin into heterochromatin or vice versa. The active genes present in euchromatin gets transcribed to make mRNA whereby further encoding the functional proteins is the main function of euchromatin. Hence they are considered as genetically and transcriptionally active. Housekeeping genes are one of the forms of euchromatin. 11
