Histone-modifying enzymes

These nucleosomes further fold together into highly condensed chromatin, which renders the organism's genetic material far less accessible to the factors required for gene transcription, DNA replication, recombination and repair.The positive charge on a histone is always neutralized upon acetylation, creating euchromatin which increases transcription and expression of the target gene.Histone methylation is responsible for either activation or repression of genes, depending on the target site, and plays an important role in development and learning.[citation needed] Additionally, the phosphorylation of histones has been found to play a role in DNA repair and chromatin condensation during cell division.[29] ADPr is an important mechanism in gene regulation that affects chromatin organization, the binding of transcription factors, and mRNA processing through poly-ADP ribose polymerase (PARP) enzymes.PARP-1 binds histones near the axis where DNA enters and exits the nucleosome and additionally interacts with numerous chromatin-associated proteins which allow for indirect association with chromatin.[36] Fpr4 is the prolyl isomerase enzyme (PPIase) which converts the amino acid proline (P) on histones between the cis and trans conformations.Conversely, the trans position of P38 promotes a more open histone conformation, allowing for K36 methylation and leading to an increase gene transcription.[36] Alterations in the functions of histone-modifying enzymes deregulate the control of chromatin-based processes, ultimately leading to oncogenic transformation and cancer.[40] Vitamin B12 deficiency in mice has been shown to alter expression of histone modifying enzymes in the brain, leading to behavioral changes and epigenetic reprogramming.
DNA is wrapped around histones to form nucleosomes . Nucleosomes are shown as " beads on a string " with the distinction between euchromatin and heterochromatin .
The basic units of chromatin structure.
The dynamic state of histone acetylation/deacetylation regulated by HAT and HDAC enzymes; acetylation of histones alters accessibility of chromatin.
A phosphoryl group is shown in blue.
An O-GlcNAcylated threonine residue. The GlcNAc moiety is shown in red while the modified threonine is shown in black.
An adenosine diphosphate ribose group.
The amino acid arginine (left) is converted to citrulline (right) via the process of citrullination .
Proline trans-cis isomerization by a PPIase enzyme.
histonesnucleosomesbeads on a stringeuchromatinheterochromatinchromatinenzymesmodificationhistoneprotein translationgene expressioneukaryoticgenomeproteinsgene transcriptionDNA replicationrecombinationrepairhistone modificationpost-translational modificationcovalently attachingtranscriptionacetylationmethylationphosphorylationubiquitinationfunctional groupO-GlcNAcylationsumoylationADP-ribosylationcitrullinationproline isomerizationRNA polymerase control by chromatin structureHistone acetyltransferases (HATs)Histone deacetylases (HDACs)Histone methyltransferases (HMTs)demethylasesProtein kinases (PTKs)Protein phosphatases (PPs)Ubiquitin ligasesDeubiquitinating enzymes (DUBs)Histone acetylationacetyl grouplysine (K)N-terminalHistone methylationmethyl groupsarginine (R)phosphoryl groupHistone phosphorylationserine (S)threonine (T)tyrosine (Y)amino-acidDNA repairchromatin condensationcell divisiondouble-stranded breaksubiquitin proteinshistone H2AXDNA damagedouble-strand breaksO-GlcNAc transferase (OGT)O-GlcNAcase (OGA)Poly-ADP ribose polymeraseProtein arginine deiminaseO-GlcNAcylatedthreonineGlcNAcO-GlcNAcylation (O-GlcNAc)Small Ubiquitin-like Modifier (SUMO) proteinsthree main stepsconjugationligationheterodimermulti-protein complextranscription factorsbase excision repairnucleotide excision repairnon-homologous end joininghomologous recombinationadenosine diphosphate riboseADP-ribosylation (ADPr)adenosine diphosphate ribose (ADP-ribose) groupsproteingene regulationmRNA processingpoly-ADP ribose polymerase (PARP) enzymesDNA fragmentssingle-stranded breakstranscription coregulatorDNA methylationDNA methyltransferaseargininecitrullineamino acidProtein arginine deiminases (PADs)ketimineketonetrans-cis isomerizationPPIaseIsomerizationprolyl isomerase enzyme (PPIase)proline (P)cis and trans conformationscatalytic activityN-terminal regiononcogeniccancerepigenetictumourigenesisVitamin B12lipid metabolismpathophysiologyNucleosomeHistone acetylation and deacetylationProtein phosphorylationUbiquitinO-GlcNAcProline isomerization in epigeneticsBibcode