page_title: Formylation
section_title: Formylation in Histone Proteins
hierarchical_section_title: Formylation / Formylation reactions in biology / Formylation in Histone Proteins
caption_attribution_description: English: mechanism of formyl phosphate formation due to DNA damage
context_page_description: In biochemistry, the addition of a formyl functional group is termed formylation. A formyl functional group consists of a carbonyl bonded to hydrogen. When attached to an R group, a formyl group is called an aldehyde.
  Formylation has been identified in several critical biological processes. Methionine was first discovered to be formylated in E. coli by Marcker and Sanger in 1964 and was later identified to be involved in the initiation of protein synthesis in bacteria and organelles. The formation of N-formylmethionine is catalyzed by the enzyme methionyl-tRNAᴹᵉᵗ transformylase. Additionally, two formylation reactions occur in the de novo biosynthesis of purines. These reactions are catalyzed by the enzymes glycinamide ribonucleotide transformylase and 5-aminoimidazole-4-carboxyamide ribotide transformylase. More recently, formylation has been discovered to be a histone modification, which may modulate gene expression.
context_section_description: ε-Formylation is one of many post-translational modifications that occur on histone proteins, which been shown to modulate chromatin conformations and gene activation.
  Formylation has been identified on the Nε of lysine residues in histones and proteins. This modification has been observed in linker histones and high mobility group proteins, it is highly abundant and it is believed to have a role in the epigenetics of chromatin function. Lysines that are formylated have been shown to play a role in DNA binding. Additionally, formylation has been detected on histone lysines that are also known to be acetylated and methylated. Thus, formylation may block other post-translational modifications.
  Formylation is detected most frequently on 19 different modification sites on Histone H1. The genetic expression of the cell is highly disrupted by formylation, which may cause diseases such as cancer. The development of these modifications may be due to oxidative stress.
  In histone proteins, lysine is typically modified by Histone Acetyl-Transferases (HATs) and Histone Deacetylases (HDAC or KDAC).
  The acetylation of lysine is fundamental to the regulation and expression of certain genes. Oxidative stress creates a significantly different environment in which acetyl-lysine can be quickly outcompeted by the formation of formyl-lysine due to the high reactivity of formylphosphate species. This situation is currently believed to be caused by oxidative DNA damage.
  A mechanism for the formation of formylphosphate has been proposed, which it is highly dependent on oxidatively damaged DNA and mainly driven by radical chemistry within the cell. The formylphosphate produced can then be used to formylate lysine. Oxidative stress is believed to play a role in the availability of lysine residues in the surface of proteins and the possibility of being formylated.
caption: Formyl phosphate is a proposed product of oxidative DNA damage.
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