Editing Histone octamer (section)

==The histone octamer in molecular detail==

Core [[histones]] are four [[proteins]] called H2A, H2B, H3 and H4 and they are all found in equal parts in the cell.  All four of the core histone [[amino acid]] sequences contain between 20 and 24% of [[lysine]] and [[arginine]] and the size or the protein ranges between 11400 and 15400 daltons, making them relatively small, yet highly positively charged proteins.<ref name=watson />  High content of positively charged amino acids allow them to closely associate with negatively charged [[DNA]].  Heterodimers, or histone-only intermediates are formed from histone-fold domains.  The formation of histone only-intermediates proceeds when core histones are paired into the interlocked crescent shape quasi-symmetric heterodimer.  Each histone fold domain is composed of 3 [[α-helix]] regions that are separated by disordered loops.  The histone fold domain is responsible for formation of head-to-tail heterodimers of two histones: H2A-H2B and H3-H4.  However, H3 and H4 histones first form a heterodimer and then in turn the heterodimer dimerizes to form a tetramer (H3-H4)<sub>2</sub>.<ref name="Structure and dynamic behavior of nucleosomes">{{cite journal|last=Luger|first=Karolin|title=Structure and dynamic behavior of nucleosomes|journal=Current Opinion in Genetics & Development|date=April 2003|volume=13|issue=2|pages=127–135|doi=10.1016/S0959-437X(03)00026-1|pmid=12672489}}</ref>  The heterodimer formation is based on the interaction of hydrophobic amino acid residue interactions between the two proteins.<ref name="Structure and dynamic behavior of nucleosomes"/>

Quasi symmetry allows the heterodimer to be superimposed on itself by a 180 degree rotation around this symmetry axis.  As a result of the rotation, two ends of histones involved in DNA binding of the crescent shape H3-H4 are equivalent, yet they organize different stretches of DNA.  The H2A-H2B dimer also folds similarly.  The (H3-H4)<sub>2</sub> tetramer is wrapped with DNA around it as a first step of nucleosome formation.  Then two H2A-H2B dimers are connected to the DNA-(H3-H4)<sub>2</sub> complex to form a nucleosome.<ref name=H2A-H2B>{{cite journal|last=D’Arcy|first=Sheena|author2=Martin, Kyle W. |author3=Panchenko, Tanya |author4=Chen, Xu |author5=Bergeron, Serge |author6=Stargell, Laurie A. |author7=Black, Ben E. |author8= Luger, Karolin |title=Chaperone Nap1 Shields Histone Surfaces Used in a Nucleosome and Can Put H2A-H2B in an Unconventional Tetrameric Form|journal=Molecular Cell|date=September 2013|volume=51|issue=5|pages=662–677|doi=10.1016/j.molcel.2013.07.015 |pmid=23973327 |pmc=3878309}}</ref>

Each of the four core histones, in addition to their histone-fold domains, also contain flexible, unstructured extensions called [[histone]] “tails”.<ref name=H1>{{cite journal|last=Harshman|first=S. W.|author2=Young, N. L. |author3=Parthun, M. R. |author4= Freitas, M. A. |title=H1 histones: current perspectives and challenges|journal=Nucleic Acids Research|date=14 August 2013|doi=10.1093/nar/gkt700 |volume=41 |issue=21|pages=9593–9609 |pmid=23945933 |pmc=3834806}}</ref>  Treatment of nucleosomes with [[protease]] [[trypsin]] indicates that after histone tails are removed, DNA is able to stay tightly bound to the nucleosome.<ref name=watson />  Histone tails are subject to a wide array of modifications which includes [[phosphorylation]], [[acetylation]], and [[methylation]] of serine, lysine and arginine residues.<ref name=watson />