{"id":124,"date":"2023-03-07T15:25:44","date_gmt":"2023-03-07T15:25:44","guid":{"rendered":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/?post_type=chapter&p=124"},"modified":"2023-04-07T11:15:46","modified_gmt":"2023-04-07T11:15:46","slug":"eukaryotic-gene-organization-packaging-of-dna-to-chromosome","status":"publish","type":"chapter","link":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/chapter\/eukaryotic-gene-organization-packaging-of-dna-to-chromosome\/","title":{"raw":"Eukaryotic gene organization - Packaging of DNA to Chromosome","rendered":"Eukaryotic gene organization – Packaging of DNA to Chromosome"},"content":{"raw":"

Histones\u00a0<\/strong><\/span><\/h1>\r\n

[pb_glossary id=\"909\"]Histones [\/pb_glossary]are basic proteins. Histones are enriched with basic lysine and arginine residues, Their positive charges enables\u00a0 them to associate with the negatively charged DNA ( due to the phosphates , PO4 -<\/sup> ) . The histones function as spools for the thread-like DNA to wrap around. Histones may be chemically modified through the action of enzymes to regulate gene expression. Core histones share a structural motif known as the histone fold domain, formed by three \u03b1-helices connected by two loops.<\/span><\/p>\r\n

Types of Histones\u00a0<\/strong><\/p>\r\n

Basically histones are of two category namely<\/p>\r\n

Core histone\u00a0 which includes\u00a0 H2A, H2B, H3 & H4 <\/strong>and\u00a0 <\/span>Linker histone\u00a0 which includes H1.<\/strong><\/p>\r\n

H2A<\/strong> is the core histone with the largest number of variants. The histone H2A variants which are found in most eukaryotes are H2AZ and H2AX.\u00a0Phosphorylation of H2AX has been found to aid in the recruitment of proteins involved in DNA repair<\/span><\/p>\r\n

Histone H2B<\/strong> variants are few in number and\u00a0 have specialized roles in chromatin compaction during gametogenesis<\/span><\/p>\r\n

Histone H<\/strong>3 variants include H3.3, CenHS and H3.4. H3.3\u00a0 is found in transcriptionally active chromatin\u00a0<\/span><\/p>\r\n

Histone H4<\/strong> is the most highly conserved histone. H4 makes extensive contacts with the other three core histones in the nucleosome core particle\u00a0<\/span><\/p>\r\n\r\n

Gene Organization in Eukaryotes\u00a0<\/strong><\/span><\/h1>\r\n

The large eukaryotic genome or DNA approximately 2 m in length is packed\u00a0 in to a nucleus of roughly 10 \u00b5m diameter through an orderly packaging.<\/p>\r\n

Nucleosomes<\/strong><\/p>\r\n

Nucleosomes are the basic unit of DNA packaging in eukaryotes and represent the first level of chromatin organization. A nucleosome consist of a segment of DNA wound around a\u00a0 \u00a0protein core called -<\/span>histone octamer.<\/strong> This structure is often compared to thread wrapped around a spool. <\/span><\/p>\r\n

The nucleosome core particle consists of approximately 146- 147 base pairs of DNA\u00a0 wrapped\u00a0 around a histone octamer , consisting of 2 copies each of the core histones namely\u00a0 <\/span>H2A, H2B, H3, and H4.<\/strong>The octamer structure is a four-helix bundle comprised of two H3-H4 and two H2A-H2B dimers. <\/span><\/p>\r\n

Nucleosome cores are separated by linker DNA<\/strong> of variable length ( 20 to 80 base pairs of linker DNA ) and are associated with the linker histone H1<\/strong>. Nucleosomes connected by a DNA linker of variable\u00a0 forms a 10-nm beads-on-a-string array.<\/strong><\/span>\u00a0<\/span><\/p>\r\n

Nucleosomes\u00a0 pack DNA in a sequence-independent fashion.\u00a0<\/strong>The core histones make contact with the DNA primarily through <\/span>three to six hydrogen bonds between the protein main chain amides and the DNA phosphate backbone.<\/span><\/p>\r\n

\u00a0<\/span>Nucleosome particles can be modified in their composition, structure and location by chromatin remodeling complexes <\/strong>and regulates \u00a0gene expression. <\/span>Nucleosomes are folded through a series of successively higher order structures to eventually form a chromosome. A nucleosome plus histone H1 is referred to as[pb_glossary id=\"912\"] Chromatosome<\/strong>[\/pb_glossary]\u00a0<\/strong><\/span><\/p>\r\n

The 30 nm Fibre\u00a0<\/strong><\/p>\r\n

The chromatosome fold\u00a0 up to a 30 nm fibre\u00a0.<\/strong>Nucleosome core particles can stack on top of each other to form extended structures. These stacks can adopt a gentle helical configuration.\u00a0 The 30 nm fibre\u00a0<\/span> consists of a helical array of nucleosomes, each comprising a core particle wrapping \u223c146 or 147 base pairs (bp) of DNA associated with a linker histone. Secondary structures to chromatin are demonstrated by the solenoid model and the zigzag model. The solenoid model consists of tightly wound nucleosomes containing 6 nucleosomes per turn in a regular, spiral configuration . The zigzag model is a bit looser form of chromatin with irregular configuration. In this model, nucleosomes have little face-to-face contact.<\/span><\/p>\r\n

Nuclear Scaffold\u00a0<\/strong><\/p>\r\n

Higher order packaging consisting of loops of the 30-nm fibers attached to a proteinaceous nuclear scaffold by an interaction between the scaffold and specific DNA sequences called [pb_glossary id=\"914\"]Scaffold\/matrix attachment regions (S\/MARs[\/pb_glossary]) . <\/strong>These are DNA elements that serve to compartmentalize the chromatin into structural and functional domains. <\/span><\/p>\r\n

Loops are formed averaging about 300nm in length.\u00a0 The 300nm fibre<\/strong> are compressed and folded\u00a0 producing a 250 nm wide fibre .<\/span><\/p>\r\n

Upon tight coiling of the 250nm wide fiber the chromatid of chromosome is formed.\u00a0<\/strong><\/p>\r\n

<\/p>\r\n

<\/p>","rendered":"

Histones\u00a0<\/strong><\/span><\/h1>\n

Histones <\/a>are basic proteins. Histones are enriched with basic lysine and arginine residues, Their positive charges enables\u00a0 them to associate with the negatively charged DNA ( due to the phosphates , PO4 –<\/sup> ) . The histones function as spools for the thread-like DNA to wrap around. Histones may be chemically modified through the action of enzymes to regulate gene expression. Core histones share a structural motif known as the histone fold domain, formed by three \u03b1-helices connected by two loops.<\/span><\/p>\n

Types of Histones\u00a0<\/strong><\/p>\n

Basically histones are of two category namely<\/p>\n

Core histone\u00a0 which includes\u00a0 H2A, H2B, H3 & H4 <\/strong>and\u00a0 <\/span>Linker histone\u00a0 which includes H1.<\/strong><\/p>\n

H2A<\/strong> is the core histone with the largest number of variants. The histone H2A variants which are found in most eukaryotes are H2AZ and H2AX.\u00a0Phosphorylation of H2AX has been found to aid in the recruitment of proteins involved in DNA repair<\/span><\/p>\n

Histone H2B<\/strong> variants are few in number and\u00a0 have specialized roles in chromatin compaction during gametogenesis<\/span><\/p>\n

Histone H<\/strong>3 variants include H3.3, CenHS and H3.4. H3.3\u00a0 is found in transcriptionally active chromatin\u00a0<\/span><\/p>\n

Histone H4<\/strong> is the most highly conserved histone. H4 makes extensive contacts with the other three core histones in the nucleosome core particle\u00a0<\/span><\/p>\n

Gene Organization in Eukaryotes\u00a0<\/strong><\/span><\/h1>\n

The large eukaryotic genome or DNA approximately 2 m in length is packed\u00a0 in to a nucleus of roughly 10 \u00b5m diameter through an orderly packaging.<\/p>\n

Nucleosomes<\/strong><\/p>\n

Nucleosomes are the basic unit of DNA packaging in eukaryotes and represent the first level of chromatin organization. A nucleosome consist of a segment of DNA wound around a\u00a0 \u00a0protein core called –<\/span>histone octamer.<\/strong> This structure is often compared to thread wrapped around a spool. <\/span><\/p>\n

The nucleosome core particle consists of approximately 146- 147 base pairs of DNA\u00a0 wrapped\u00a0 around a histone octamer , consisting of 2 copies each of the core histones namely\u00a0 <\/span>H2A, H2B, H3, and H4.<\/strong>The octamer structure is a four-helix bundle comprised of two H3-H4 and two H2A-H2B dimers. <\/span><\/p>\n

Nucleosome cores are separated by linker DNA<\/strong> of variable length ( 20 to 80 base pairs of linker DNA ) and are associated with the linker histone H1<\/strong>. Nucleosomes connected by a DNA linker of variable\u00a0 forms a 10-nm beads-on-a-string array.<\/strong><\/span>\u00a0<\/span><\/p>\n

Nucleosomes\u00a0 pack DNA in a sequence-independent fashion.\u00a0<\/strong>The core histones make contact with the DNA primarily through <\/span>three to six hydrogen bonds between the protein main chain amides and the DNA phosphate backbone.<\/span><\/p>\n

The 30 nm Fibre\u00a0<\/strong><\/p>\n

The chromatosome fold\u00a0 up to a 30 nm fibre\u00a0.<\/strong>Nucleosome core particles can stack on top of each other to form extended structures. These stacks can adopt a gentle helical configuration.\u00a0 The 30 nm fibre\u00a0<\/span> consists of a helical array of nucleosomes, each comprising a core particle wrapping \u223c146 or 147 base pairs (bp) of DNA associated with a linker histone. Secondary structures to chromatin are demonstrated by the solenoid model and the zigzag model. The solenoid model consists of tightly wound nucleosomes containing 6 nucleosomes per turn in a regular, spiral configuration . The zigzag model is a bit looser form of chromatin with irregular configuration. In this model, nucleosomes have little face-to-face contact.<\/span><\/p>\n

Nuclear Scaffold\u00a0<\/strong><\/p>\n

Higher order packaging consisting of loops of the 30-nm fibers attached to a proteinaceous nuclear scaffold by an interaction between the scaffold and specific DNA sequences called Scaffold\/matrix attachment regions (S\/MARs<\/a>) . <\/strong>These are DNA elements that serve to compartmentalize the chromatin into structural and functional domains. <\/span><\/p>\n

Loops are formed averaging about 300nm in length.\u00a0 The 300nm fibre<\/strong> are compressed and folded\u00a0 producing a 250 nm wide fibre .<\/span><\/p>\n

Upon tight coiling of the 250nm wide fiber the chromatid of chromosome is formed.\u00a0<\/strong><\/p>\n

\n

\n

definition<\/span>

\u00a0<\/span>Nucleosome particles can be modified in their composition, structure and location by chromatin remodeling complexes <\/strong>and regulates \u00a0gene expression. <\/span>Nucleosomes are folded through a series of successively higher order structures to eventually form a chromosome. A nucleosome plus histone H1 is referred to as Chromatosome<\/strong><\/a>\u00a0<\/strong><\/span><\/p>\n