Editing Histone (section)

===Addiction===

Epigenetic modifications of histone tails in specific regions of the brain are of central importance in addictions.<ref name=RobisonNestler>{{cite journal | vauthors = Robison AJ, Nestler EJ | title = Transcriptional and epigenetic mechanisms of addiction | journal = Nature Reviews. Neuroscience | volume = 12 | issue = 11 | pages = 623–637 | date = October 2011 | pmid = 21989194 | pmc = 3272277 | doi = 10.1038/nrn3111 }}</ref><ref>{{cite journal | vauthors = Hitchcock LN, Lattal KM | title = Histone-mediated epigenetics in addiction | journal = Progress in Molecular Biology and Translational Science | volume = 128 | pages = 51–87 | date = 2014 | pmid = 25410541 | pmc = 5914502 | doi = 10.1016/B978-0-12-800977-2.00003-6 | publisher = Academic Press | isbn = 9780128009772 }}</ref><ref>{{cite journal | vauthors = McQuown SC, Wood MA | title = Epigenetic regulation in substance use disorders | journal = Current Psychiatry Reports | volume = 12 | issue = 2 | pages = 145–153 | date = April 2010 | pmid = 20425300 | pmc = 2847696 | doi = 10.1007/s11920-010-0099-5 }}</ref>  Once particular epigenetic alterations occur, they appear to be long lasting "molecular scars" that may account for the persistence of addictions.<ref name=RobisonNestler />

[[Cigarette#consumtpion|Cigarette]] smokers (about 15% of the US population) are usually addicted to [[nicotine]].<ref>{{Cite web | url=https://www.drugabuse.gov/publications/tobacco-nicotine-e-cigarettes/nicotine-addictive | title=Is nicotine addictive?}}</ref>  After 7 days of nicotine treatment of mice, acetylation of both histone H3 and histone H4 was increased at the FosB promoter in the [[nucleus accumbens]] of the brain, causing 61% increase in FosB expression.<ref>{{cite journal | vauthors = Levine A, Huang Y, Drisaldi B, Griffin EA, Pollak DD, Xu S, Yin D, Schaffran C, Kandel DB, Kandel ER | title = Molecular mechanism for a gateway drug: epigenetic changes initiated by nicotine prime gene expression by cocaine | journal = Science Translational Medicine | volume = 3 | issue = 107 | pages = 107ra109 | date = November 2011 | pmid = 22049069 | pmc = 4042673 | doi = 10.1126/scitranslmed.3003062 }}</ref>  This would also increase expression of the [[Alternative splicing|splice variant]] [[FosB#Delta FosB|Delta FosB]].  In the [[nucleus accumbens]] of the brain, [[FosB#Delta FosB|Delta FosB]] functions as a "sustained molecular switch" and "master control protein" in the development of an [[addiction]].<ref>{{cite journal |vauthors=Ruffle JK |date=November 2014 |title=Molecular neurobiology of addiction: what's all the (Δ)FosB about? |url=https://www.tandfonline.com/doi/abs/10.3109/00952990.2014.933840?journalCode=iada20 |journal=The American Journal of Drug and Alcohol Abuse |volume=40 |issue=6 |pages=428–37 |doi=10.3109/00952990.2014.933840 |pmid=25083822 |s2cid=19157711}}</ref><ref>{{cite journal | vauthors = Nestler EJ, Barrot M, Self DW | title = DeltaFosB: a sustained molecular switch for addiction | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 20 | pages = 11042–6 | date = September 2001 | pmid = 11572966 | pmc = 58680 | doi = 10.1073/pnas.191352698 | bibcode = 2001PNAS...9811042N | doi-access = free }}</ref>

About 7% of the US population is addicted to [[Alcoholism|alcohol]].  In rats exposed to alcohol for up to 5 days, there was an increase in histone 3 lysine 9 acetylation in the pronociceptin promoter in the brain [[amygdala]] complex.  This acetylation is an activating mark for pronociceptin.  The nociceptin/nociceptin opioid receptor system is involved in the reinforcing or conditioning effects of alcohol.<ref>{{cite journal |vauthors=D'Addario C, Caputi FF, Ekström TJ, Di Benedetto M, Maccarrone M, Romualdi P, Candeletti S |date=February 2013 |title=Ethanol induces epigenetic modulation of prodynorphin and pronociceptin gene expression in the rat amygdala complex |url=https://link.springer.com/article/10.1007/s12031-012-9829-y |journal=Journal of Molecular Neuroscience |volume=49 |issue=2 |pages=312–9 |doi=10.1007/s12031-012-9829-y |pmid=22684622 |s2cid=14013417}}</ref>

[[Methamphetamine]] addiction occurs in about 0.2% of the US population.<ref>{{Cite web | url=https://www.drugabuse.gov/publications/research-reports/methamphetamine/what-scope-methamphetamine-abuse-in-united-states |title = What is the scope of methamphetamine abuse in the United States?}}</ref>  Chronic methamphetamine use causes [[Histone methylation#Function|methylation of the lysine]] in position 4 of histone 3 located at the [[Promoter (genetics)|promoters]] of the ''[[c-fos]]'' and the ''[[CCR2|C-C chemokine receptor 2]] (ccr2)'' genes, activating those genes in the nucleus accumbens (NAc).<ref name=Godino>{{cite journal | vauthors = Godino A, Jayanthi S, Cadet JL | title = Epigenetic landscape of amphetamine and methamphetamine addiction in rodents | journal = Epigenetics | volume = 10 | issue = 7 | pages = 574–80 | date = 2015 | pmid = 26023847 | pmc = 4622560 | doi = 10.1080/15592294.2015.1055441 }}</ref>  c-fos is well known to be important in [[addiction]].<ref>{{cite journal | vauthors = Cruz FC, Javier Rubio F, Hope BT | title = Using c-fos to study neuronal ensembles in corticostriatal circuitry of addiction | journal = Brain Research | volume = 1628 | issue = Pt A | pages = 157–73 | date = December 2015 | pmid = 25446457 | pmc = 4427550 | doi = 10.1016/j.brainres.2014.11.005 }}</ref>  The ''ccr2'' gene is also important in addiction, since mutational inactivation of this gene impairs addiction.<ref name=Godino />