CHROMATIN

1. CHROMATIN 100 trillion meters of DNA per human • Haploid human genome contains approximately 3 billion base pairs of DNA • each base pair is around 0.34 nanometers long • Each diploid cell therefore contains about 2 meters of DNA • Human body contains about 50 trillion cells A complex of nucleic acids and proteins (histones), which condenses to form a chromosome during cell division. cell nucleus …in eukaryotic cells, prokaryotic cells….nucleoid. • Its functions are • To package DNA into a smaller volume to fit in the cell • Strengthen the DNA to allow mitosis and meiosis • To serve as a mechanism to control gene expression.

2. Two each of the histones H2A, H2B, H3, and H4 come together to form a histone octamer, which binds and wraps about 1.7 turns of DNA, 166bp. nucleosomes are joined by 20 base pairs linker DNA The packaging of DNA into nucleosomes shortens the fiber length about sevenfold

3. EPIGENETIC EPIGENETICS is the study of changes in gene expression or cellular phenotype, caused by mechanisms other than changes in the underlying DNA sequence. EPIGENETIC TRAIT, "stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence" CHROMATIN REMODELING: is the enzyme-assisted process to facilitate access of nucleosomal DNA by remodeling the structure, composition and positioning of nucleosomes. • Generally speaking, there are two major mechanisms by which chromatin is made more accessible: • Post translational enzymatic histone modifications. primarily occur at N-terminal histone tails, affect the binding affinity between histones and DNA, and thus loosening and tightening the condensed DNA wrapped around histones. • Acetylation…loosening of chromatin ….. replication and transcription. by HAT (histone acetyl transferase); deacetylation - by HDAC (histone deacetylase) • Methylation: methylated residues hold DNA together strongly and restrict access to various enzymes, lysine and arginine residues

4. Phosphorylation: modification of proteins in which a serine, a threonine or a tyrosine residue is phosphorylated by a protein kinase , • "activate, inhibit , signaling system may be activated or inhibited, degraded by the ATP-dependent ubiquitin/proteasome pathway • Ubiquitination : "kiss of death” ubiquitin • 2- Histones displacement by chromatin remodeling complexes: • ATP-dependent chromatin-remodeling complexes regulate gene expression by either moving, ejecting or restructuring nucleosomes. These protein complexes have a common ATPase domain and energy from the hydrolysis of ATP allows these remodeling complexes to reposition (slide, twist or loop) nucleosomes along the DNA, expel histones away from DNA or facilitate exchange of histone variants, and thus creating nucleosome-free regions of DNA for gene activation. • these processes are reversible, so modified or remodeled chromatin can be returned to its compact state after transcription and/or replication are complete.

5. TYPES • in nature DNA can form three structures, A-, B- and Z-DNA. • depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases. A: a shorter more compact helical structure. occurs only in dehydrated samples of DNA, such as those used in crystallographic experiments Z:left-handed helix with a zig-zag phosphate backbone , The major and minor grooves, unlike A- and B-DNA, show little difference in width

6. CHROMATIN IMMUNOPRECIPITATION • experimental technique used to investigate the interaction between proteins and DNA in the cell. • ChIP also aims to determine the specific location in the genome that various histone modifications are associated with, indicating the target of the histone modifiers.