Genomes are larger due to less gene density -Introns dilute density -Intergenetic regions dilute density -Bacteria use one intergenetic region to regulate several correlated genes. In humans only ~5% of transcribed DNA gets translated - 95% consists of introns

DNA is wrapped around histones to form a nucelosome - first step of DNA packaging Packaging: -Allows DNA to fit into a cell (reduces length 10,000X) -Protects DNA -Makes transmission to daughter cells possible -Restricts transcription -Nucleosomes only reduce length 6x -Highly conserved structure in eukaryotes

2 copies of 4 sub units make a histone core -Each histone protein has an N- terminal tail that is not necessary for nucleosome formation -Proteins are lysine and argenine rich - positively charged

“Histone fold” domain assists in self assembly of tetramers and dimers -Each histone core protein has 3 alpha- helices separated by an unstructured loop -Nucleosome assembly is initiated by H3/H4 tetramer binding, followed by two H2A/H2B dimers -~40 hydrogen bonds are formed between histone proteins and the DNA backbone and minor groove -Helices fit into major groove, associate with DNA due to electrostatic charges

Functionally, why is it important that histones only interact with the phosphate backbone and the minor groove of DNA? - There is no sequence specific binding: Nucleosomes can form with any stretch of DNA (if it hasn’t been modified in some way)

Nucleosomes alter linkage number locally and facilitate unwinding

Histone 1 coils DNA tighter H1 absent H1 present

Angles of DNA entry and exit from nucleosomes generates a 30nm fiber of DNA Larger structure formation is also dependent on histone tails

Packaging into nucleosomes and 30nm fibers shorten DNA 40x - Need to shorten 1,000-10,000x to fit into a nucleus

DNA is looped into a nuclear scaffold - 1 loop is 40-90kb

Histone tails may be modified to allow easier access to DNA