CHROMOSOMES

Human have 23 paired chromosomes. 22 of these pairs are non-sex (autosomes or chromosomes inherited symmetrically from both parents, regardless of sex) and 1 pair are sex chromosomes (X and Y in males and XX in females) to bring the total number of chromosomes in a human somatic (non-germ line) to a total of 46.

Chromosomes have two arms, the so called long arm ("q") and the short arm ("p) which are separated by a centromere.

Chromosome Structure:

Each chromosome consists of a long DNA molecule associated with proteins that fold the DNA into a more compact structure. This complex of DNA and protein is sometimes referred to as chromatin. The proteins that bind to the DNA are typically referred to as the histones and the nonhistone proteins.

Chromatin is organized into nucleosomal subunits. Each nucleosome consists of 146 bp of DNA wrapped around two molecules each of the histone proteins H2A, H2B, H3 and H4 and a single linker protein, H1. Histones are responsible for the most basic level of chromosome organization, the nucleosome. Histone dimers form a compact octamer core.  The lenght of the DNA wound around the core has been shown to be about 150 nucleotide pairs wrapped twice around 8 histone molecules (two each of H2A, H2B, H3, and H4). Nucleosomes are separated by about 50 bp of DNA.

Many hydrogen bonds are formed between DNA (phosphodiester backbone) and the histone core (amino acid backbone). Numerous hydrophobic interactions interactions also hold DNA and protein together in the nucleosome. All the core histones are rich in lysine and arginine (2 amino acids with basic side chains) and their positive charges can neutralize the negatively charged DNA backbone. Each of the core histones has a long N-terminal amino acid tails which extends out from the DNA-histone core. The N-terminal tails of each of the histones are subject to different types of covalent modification which are crucial in regulating chromatin structure which can regulate gene expression. The domains are lysine rich are are targets of a class of enzymes termed histone acetyl transferases.

Although long strings of nucleosomes form on most chromosomal DNA, chromatin in a cell probably rarely adopts an extended beads on a string form. Instead, it is seen to be in the form of a fiber about 30 nm thick. This represents nucleosomes which are packed on top of one another, generating arrays in which the DNA is even more condensed. Such highly packed chromatin is sometimes referred to as euchromatin. The 30 nm euchromatin is not conducive to transcription (2nm and 11 nm would be compatible).

There is even a more condensed form of chromatin that is sometimes called heterochromatin which is included in certain regions of the chromosomes such as the telemores and centromeres. Covalent modification of the nucleosome core histones as by methylation of specifc lysines by histone methl transferases play a critical role in the formation of heterochromatin. One protein, Sir2, also has a role in creating a pattern of histone underacetylation unique to heterchromatin.

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