H4 core globular domain (involved in protein-protein interaction) or C-terminal tail (involved in post-translational modification). Alternative translation The Osteogenic Growth Peptide (OGP) is a 14-aa peptide produced from alternative translation of histone H4 mRNA, sharing the C-terminal sequence ALKRQGRTLYGFGG of histone H4. Translation is initiated at the 85th amino acid of the histone H4 mRNA, resulting in a 19-aa peptide (preOGP). This is converted into OGP through the cleavage of 5 amino-terminal residues. It is found in human and rat circulation as well as regenerating bone marrow. In blood serum it is bound to α2M along with two other binding proteins that are not clearly identified. A specific receptor has not been identified, but some signaling pathways involved in its bone-regenaration function has been elucidated. Post-translational modifications Eukaryotic organisms can produce small amounts of specialized variant core histones that differ in amino acid sequence from the main ones. These variants with a variety of covalent modifications on the N-terminal can be added to histones making possible different chromatin structures that are required for DNA function in higher eukaryotes. Potential modifications include methylation (mono-, di-, or tri-methylation) or acetylation on the tails. Methylation Histone methylation occurs on arginine, lysine and histidine amino acids residues. Mono-, di- or tri-methylation has been discovered on histone H2A, H3 and H4. Histone methylation has been associated with various cellular functions such as transcription, DNA replication, and DNA damage response including repair, heterochromatin formation, and somatic cell reprogramming. Among these biological functions, transcriptional repression and activation are the most studied. Studies have shown that H4R3 methylation by PRMT1 (a histone methyltransferase) appears to be essential in vivo for the establishment or maintenance of a wide range of “active” chromatin modifications. Also methylation of histone H4 by PRMT1 was sufficient to permit subsequent acetylation on the N-terminal tail. However, acetylation of H4 inhibits its methylation by PRMT1. Acetylation Acetylation of histones is thought to relax condensed heterochromatin as the negative charge of acetyl groups can repel the DNA phosphate backbone charges, thus reducing the histone binding affinity for DNA. This hypothesis was validated by the discovery of the histone acetyltransferase (HAT) activity of several transcriptional activator complexes. Histone acetylation influences chromatin structure in several ways. First, it can provide a tag for the binding of proteins that contain areas which recognize the acetylated tails. Secondly, it can block the function of chromatin remodelers. Thirdly, it neutralizes the