Chromatin Structure Lecture Notes PDF

Dr. Rami Elshazli  Packing of DNA Associate Professor of Biochemistry and Molecular Genetics  Eukaryotic chromosome:  Individual eukaryotic chromosomes contain enormous amounts of DNA.  Eukaryotic chromosome consists of a single, extremely...

Dr. Rami Elshazli  Packing of DNA Associate Professor of Biochemistry and Molecular Genetics  Eukaryotic chromosome:  Individual eukaryotic chromosomes contain enormous amounts of DNA.  Eukaryotic chromosome consists of a single, extremely long molecule of DNA.  Chromatin structure  Eukaryotic DNA is closely associated with proteins, creating chromatin.  Two basic types of chromatin:  Euchromatin.  Heterochromatin.  Euchromatin constitutes the chromosomal material.  Heterochromatin presents at the centromeres and telomeres.  The most abundant proteins in chromatin are the histones.  Dr. Rami Elshazli  Chromatin structure Associate Professor of Biochemistry and Molecular Genetics  The histones are small, positively charged proteins of five major types: H1, H2A, H2B, H3, and H4.  All histones have a high percentage of arginine and lysine, positively charged amino acids that give the histones a net positive charge.  The positive charges attract the negative charges on the phosphates of DNA.  This attraction holds the DNA in contact with the histones.  Nonhistone chromosomal protein such as chromosomal scaffold proteins may help in folding and packing the chromosome.  DNA is complexed to proteins called chromatin, that is the material makes up eukaryotic chromosomes.  The most abundant of these proteins are the five types of positively charged histone proteins: H1, H2A, H2B, H3, and H4.  Chromatin structure: Nucleosome Dr. Rami Elshazli Associate Professor of Biochemistry and Molecular Genetics  The nucleosome Chromatin has a highly complex structure with several levels of organization.  The simplest level is the double-helical structure of DNA.  Nucleosome:  The repeating core of protein and DNA is the simplest level of chromatin structure, the nucleosome.  The nucleosome is a core particle consisting of DNA wrapped about two times around an octamer of eight histone proteins (two copies each of H2A, H2B, H3, and H4).  This wrapping resembles a thread wound around a spool.  The DNA in direct contact with the histone octamer is between 145 and 147 bp in length.  Chromatin structure: Nucleosome  The histone proteins has a flexible “tail,” containing from 11 to 37 amino acids, that extends out from the nucleosome.  The fifth type of histone (H1) is not a part of the core particle but plays an important role in the nucleosome structure.  H1 binds to 20 to 22 bp of DNA where the DNA joins and leaves the octamer histone.  It helps to lock the DNA into place, acting as a clamp around the nucleosome octamer. Dr. Rami Elshazli Associate Professor of Biochemistry and Molecular Genetics  Chromatin structure: Nucleosome  Chromatosome:  The nucleosome octamer and its associated H1 histone are called the chromatosome.  Each chromatosome encompasses about 167 bp of DNA.  Chromatosomes are located at regular intervals along the DNA molecule and are separated from one another by linker DNA.  Linker DNA comprises from about 30 to 40 bp.  Nonhistone chromosomal proteins may be associated with:  The linker DNA.  Bind directly to the core particle of nucleosome octamer. Dr. Rami Elshazli Associate Professor of Biochemistry and Molecular Genetics  High order of chromatin structure  Nucleosomes fold on themselves to form a dense, tightly packed structure that makes up a fiber with a diameter of about 30 nm.  The next-higher level of chromatin structure is a series of loops of 30-nm fibers.  Each loop encompasses 20,000 to 100,000 bp of DNA and is about 300 nm in length.  The 300-nm loops are compressed and folded to produce a 250-nm-wide fiber.  Tight helical coiling of the 250-nm fiber produces the chromatid of a chromosome, approximately 700 nm in width.  The nucleosome consists of a core particle of eight histone proteins.  Chromatosomes, which are nucleosomes bound to an H1 histone, are separated by linker DNA. Dr. Rami Elshazli Associate Professor of Biochemistry and Molecular Genetics   Centromere Structure  The centromere is a constricted region of the chromosome to which spindle fibers attach.  Centromeres display considerable variation in structure.  Function of centromere:  It is essential for proper chromosome movement in mitosis and meiosis.  Centromeric sequences are the binding sites for the kinetochore, to which spindle fibers attach. Dr. Rami Elshazli Associate Professor of Biochemistry and Molecular Genetics   Telomere Structure  Telomeres are the natural ends of a chromosome.  Telomeres are region of repetitive nucleotide sequences that stabilized the ends of linear chromosomes.  Function of telomeres:  Telomeres serve as a cap that stabilizes the chromosome, much like the plastic tips on the ends of a shoelace that prevent the lace from unraveling.  Telomeres also provide a means of replicating the ends of the chromosome.  These telomeric sequences consist of a series of guanine nucleotides followed by several adenine or thymine nucleotides or both.  The repeating unit in human telomeres is 5’-TTAGGG-3’, which may be repeated from 250 to 1500 times.  Telomere shortening refers to the process of the gradual reduction in the length of telomeres associated with aging. Dr. Rami Elshazli Associate Professor of Biochemistry and Molecular Genetics  Dr. Rami Elshazli  Chromatin vs. Chromatid Associate Professor of Biochemistry and Molecular Genetics  Chromatin is a complex of DNA and protein found in eukaryotic cells.  Its primary function is to package long DNA molecules into more compact, denser structures.  Chromatid is one half of a duplicated chromosome.  Chromosomes are thread-like structures located inside the nucleus and made of protein and a single molecule of deoxyribonucleic acid (DNA). Chromosome Chromatin Chromosomes are condensed chromatin Chromatin is composed of nucleosomes, fibers. which are a complex of DNA and proteins. Chromosomes are thick and compact Chromatin is a thin and long fiber. structure. Distinctly visible during cell division. Found throughout the cell cycle.