View source for MECP2

{{Short description|DNA-binding protein involved in methylation}}
{{Infobox_gene}}
'''''MECP2''''' ('''methyl CpG binding protein 2''') is a [[gene]]<ref name="pmid10508514">{{cite journal |vauthors=Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY |author-link6=Huda Zoghbi| title = Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2 | journal = Nat. Genet. | volume = 23 | issue = 2 | pages = 185–8 |date=October 1999 | pmid = 10508514 | doi = 10.1038/13810 |s2cid=3350350}}</ref> that encodes the [[protein]] MECP2.<ref name="pmid1606614">{{cite journal |vauthors=Lewis JD, Meehan RR, Henzel WJ, Maurer-Fogy I, Jeppesen P, Klein F, Bird A | title = Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA | journal = Cell | volume = 69 | issue = 6 | pages = 905–14 |date=June 1992 | pmid = 1606614 | doi = 10.1016/0092-8674(92)90610-O| s2cid = 6825994 }}</ref> MECP2 appears to be essential for the normal function of [[nerve cell]]s. The protein seems to be particularly important for mature nerve cells, where it is present in high levels. The MECP2 protein is likely to be involved in turning off ("repressing" or "[[gene silencing|silencing]]") several other genes. This prevents the genes from making proteins when they are not needed. Recent work has shown that MECP2 can also activate other genes.<ref>{{cite journal |journal= Science |year=2008 |title= MECP2, a key contributor to neurological disease, activates and represses transcription  |vauthors=Chahrour M, etal |pmid=18511691 |volume= 320 |issue= 5880 |pages= 1224–9 |doi= 10.1126/science.1153252 |pmc= 2443785|bibcode=2008Sci...320.1224C }}</ref> The ''MECP2'' gene is located on the long (q) arm of the [[X chromosome]] in band 28 ("Xq28"), from [[base pair]] 152,808,110 to base pair 152,878,611.

MECP2 is an important reader of DNA methylation. Its methyl-CpG-binding (MBD) domain recognizes and binds [[5-mC]] regions.  MECP2 is X-linked and subject to [[X inactivation]].  MECP2 gene mutations are the cause of most cases of [[Rett syndrome]], a progressive neurologic developmental disorder and one of the most common causes of cognitive disability in females.<ref>{{cite web | title = Entrez Gene: MECP2 methyl CpG binding protein 2 (Rett syndrome)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4204}}</ref> At least 53 disease-causing mutations in this gene have been discovered.<ref name = "Šimčíková_2019 - supplementary table S7">{{cite journal | vauthors = Šimčíková D, Heneberg P | title = Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 18577 | date = December 2019 | pmid = 31819097 | pmc = 6901466 | doi = 10.1038/s41598-019-54976-4| bibcode = 2019NatSR...918577S }}</ref>

== Function ==

MECP2 protein is found in all [[cell (biology)|cell]]s in the body, including the [[brain]], acting as a transcriptional repressor and activator, depending on the context. However, the idea that MECP2 functions as an activator is relatively new and remains controversial.<ref name="pmid18511680">{{cite journal |vauthors=Cohen S, Zhou Z, Greenberg ME | title = Medicine. Activating a repressor. | journal = Science | volume = 320 | issue = 5880 | pages = 1172–3 |date=May 2008 | pmid = 18511680 | doi = 10.1126/science.1159146 | pmc = 2857976 }}</ref> In the brain, it is found in high concentrations in [[neuron]]s and is associated with maturation of the [[central nervous system]] (CNS) and in forming [[Chemical synapse|synaptic contacts]].<ref>{{cite journal |vauthors=Luikenhuis S, Giacometti E, Beard CF, Jaenisch R |title=Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue=16 |pages=6033–8 |date=April 2004 |pmid=15069197 |pmc=395918 |doi=10.1073/pnas.0401626101 |bibcode=2004PNAS..101.6033L |doi-access=free }}</ref>

== Mechanism of action ==

The MeCP2 protein binds to forms of [[DNA]] that have been [[methylated]]. The MeCP2 protein then interacts with other proteins to form a complex that turns off the gene.  MeCP2 prefers to bind to sites on the genome with a chemical alteration made to a [[cytosine]] (C) when it occurs in a particular DNA sequence, "[[CpG site|CpG]]". This is a form of [[DNA methylation]]. Many genes have [[CpG island]]s, which frequently occur near the beginning of the gene. MECP2 does not bind to these islands in most cases, as they are not methylated. The [[Gene expression|expression]] of a few genes may be regulated through methylation of their CpG island, and MECP2 may play a role in a subset of these. Researchers have not yet determined which genes are targeted by the MeCP2 protein, but such genes are probably important for the normal function of the central nervous system. However, the first large-scale mapping of MECP2 binding sites in neurons found that only 6% of the binding sites are in CpG islands, and that 63% of MECP2-bound promoters are actively expressed and only 6% are highly methylated, indicating that MECP2's main function is something other than silencing methylated promoters.<ref name="pmid18042715">{{cite journal |vauthors=Yasui DH, Peddada S, Bieda MC, Vallero RO, Hogart A, Nagarajan RP, Thatcher KN, Farnham PJ, Lasalle JM | title = Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 104 | issue = 49 | pages = 19416–21 |date=December 2007 | pmid = 18042715 | pmc = 2148304 | doi = 10.1073/pnas.0707442104 | bibcode = 2007PNAS..10419416Y | doi-access = free }}</ref>

Once bound, MeCP2 will condense the [[chromatin]] structure, form a complex with [[histone deacetylase]]s (HDAC), or block [[transcription factors]] directly. More recent studies have demonstrated that MeCP2 may also function as a transcriptional activator, through recruiting the transcription factor [[CREB1]]. This was an unexpected finding which suggests that MeCP2 is a key transcriptional regulator with potentially dual roles in gene expression. In fact, the majority of genes that are regulated by MeCP2 appear to be activated rather than repressed.<ref name="pmid18511691">{{cite journal |vauthors=Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY | title = MeCP2, a key contributor to neurological disease, activates and represses transcription | journal = Science | volume = 320 | issue = 5880 | pages = 1224–9 |date=May 2008 | pmid = 18511691 | pmc = 2443785 | doi = 10.1126/science.1153252 | bibcode = 2008Sci...320.1224C }}</ref> However, it remains controversial whether MeCP2 regulates these genes directly or whether these changes are secondary in nature.<ref name="pmid18511680"/> Further studies have shown MeCP2 may be able to bind directly to un-methylated DNA in some instances.<ref name="pmid12788925">{{cite journal |vauthors=Georgel PT, Horowitz-Scherer RA, Adkins N, Woodcock CL, Wade PA, Hansen JC | title = Chromatin compaction by human MeCP2. Assembly of novel secondary chromatin structures in the absence of DNA methylation | journal = J. Biol. Chem. | volume = 278 | issue = 34 | pages = 32181–8 |date=August 2003 | pmid = 12788925 | doi = 10.1074/jbc.M305308200 | doi-access = free }}</ref> MeCP2 has been implicated in regulation of imprinted genes and loci that include ''[[UBE3A]]'' and ''[[Dlx (gene)|DLX5]]''.<ref name="pmid17486180">{{cite journal | author = LaSalle JM | title = The odyssey of MeCP2 and parental imprinting | journal = Epigenetics | volume = 2 | issue = 1 | pages = 5–10 | year = 2007 | pmid = 17486180 | pmc = 1866173 | doi = 10.4161/epi.2.1.3697}}</ref>

Reduced expression of MECP2 in Mecp2+/- [[neural stem cell]]s causes an increase in [[cellular senescence|senescence]], impairment of proliferative capacity and accumulation of unrepaired [[DNA damage (naturally occurring)|DNA damage]].<ref name="pmid29563495">{{cite journal |vauthors=Alessio N, Riccitiello F, Squillaro T, Capasso S, Del Gaudio S, Di Bernardo G, Cipollaro M, ((Melone MAB)), Peluso G, Galderisi U |title=Neural stem cells from a mouse model of Rett syndrome are prone to senescence, show reduced capacity to cope with genotoxic stress, and are impaired in the differentiation process |journal=Exp. Mol. Med. |volume=50 |issue=3 |pages=1 |date=March 2018 |pmid=29563495 |pmc=6118406 |doi=10.1038/s12276-017-0005-x }}</ref>  After treatment of Mecp2+/- cells with any of three different DNA damaging agents, the cells accumulated more damaged DNA and were more prone to cell death than control cells.<ref name="pmid29563495" />  It was concluded that reduced MECP2 expression causes reduced capacity to [[DNA repair|repair DNA]] and this likely contributes to neurological decline.<ref name="pmid29563495" />

== Structure ==

MECP2 is part of a family of methyl-CpG-binding domain proteins (MBD), but possesses its own unique differences which help set it apart from the group.  It has two functional domains:
* a methyl-[[cytosine]]-binding domain (MBD) composed of 85 [[amino acid]]s; and
* a transcriptional repression domain (TRD) composed of 104 amino acids

The MBD domain forms a wedge and attaches to the methylated CpG sites on the DNA strands.  The TRD region then reacts with SIN3A to recruit histone deacetylases (HDAC).<ref name="pmid10518942">{{cite journal |vauthors=Wakefield RI, Smith BO, Nan X, Free A, Soteriou A, Uhrin D, Bird AP, Barlow PN | title = The solution structure of the domain from MeCP2 that binds to methylated DNA | journal = J. Mol. Biol. | volume = 291 | issue = 5 | pages = 1055–65 |date=September 1999 | pmid = 10518942 | doi = 10.1006/jmbi.1999.3023 }}</ref>  There are also unusual, repetitive sequences found at the carboxyl terminus.  This region is closely related to the fork head family, at the amino acid level.<ref>{{cite journal |url=http://www.instruct1.cit.cornell.edu/courses/bioap475/wade3.pdf |title=Methyl CpG-binding proteins and transcriptional repression |author=Paul A. Wade |journal=BioEssays |date=December 2001 |volume=23 |issue=12 |pages=1131–1137 |url-status=dead |archive-url=https://web.archive.org/web/20070814102925/http://instruct1.cit.cornell.edu/courses/bioap475/wade3.pdf |archive-date=2007-08-14 |doi=10.1002/bies.10008 |pmid=11746232 |s2cid=37525856 }}</ref>

== Role in disease ==

The role of MECP2 in disease is primarily associated with either a loss of function (under expression) of the ''MECP2'' gene as in [[Rett syndrome]] or in a gain of function (over expression) as in [[MECP2 duplication syndrome]].  Many mutations have been associated with loss of expression of the MECP2 gene and have been identified in Rett syndrome patients. These mutations include changes in single DNA [[base pair]]s ([[Single-nucleotide polymorphism|SNP]]), insertions or deletions of DNA in the ''MECP2'' gene, and changes that affect how the gene information is processed into a protein ([[RNA splicing]]). Mutations in the gene alter the structure of the MeCP2 protein or lead to reduced amounts of the protein. As a result, the protein is unable to bind to DNA or turn other genes on or off. Genes that are normally repressed by MeCP2 remain active when their products are not needed. Other genes that are normally activated by MeCP2 remain inactive leading to a lack of gene product. This defect probably disrupts the normal functioning of nerve cells, leading to the signs and symptoms of Rett syndrome.

[[Rett syndrome]] is mainly found in girls with a [[prevalence]] of around 1 in every 10,000; male fetuses with normal karyotypes afflicted with this condition rarely survive to term and if so, usually die shortly after birth.  Patients are born with very hard to find signs of a disorder, but after about six months to a year and half, speech and motor function capabilities start to decrease.  This is followed by [[seizure]]s, growth retardation and cognitive and motor impairment.<ref name="pmid15809268">{{cite journal |vauthors=Caballero IM, Hendrich B | title = MeCP2 in neurons: closing in on the causes of Rett syndrome | journal = Hum. Mol. Genet. | volume = 14 Spec No 1 | pages = R19–26 |date=April 2005 | pmid = 15809268 | doi = 10.1093/hmg/ddi102 | doi-access = free }}</ref> The MECP2 locus is [[X-linked]] and the disease-causing alleles are [[Dominance relationship|dominant]]. Due to its prevalence in females, it has been linked to male lethality, or to a predominant transmission with the paternal X chromosome; nevertheless, in rare cases some males can also be affected by Rett syndrome.<ref name="pmid14734626">{{cite journal |vauthors=Samaco RC, Nagarajan RP, Braunschweig D, LaSalle JM | title = Multiple pathways regulate MeCP2 expression in normal brain development and exhibit defects in autism-spectrum disorders | journal = Hum. Mol. Genet. | volume = 13 | issue = 6 | pages = 629–39 |date=March 2004 | pmid = 14734626 | doi = 10.1093/hmg/ddh063 | doi-access = free }}</ref> Males with gene duplications of MECP-2 at the Xq28 locus are also at risk for recurrent infections & meningitis in infancy.

Mutations in the ''MECP2'' gene have also been identified in people with several other disorders affecting the central nervous system. For example, ''MECP2'' mutations are associated with some cases of moderate to severe X-linked mental retardation. Mutations in the gene have also been found in males with severe brain dysfunction ([[neonatal encephalopathy]]) who live only into early childhood. In addition, several people with features of both Rett syndrome and [[Angelman syndrome]] (a condition characterized by mental retardation, problems with movement, and inappropriate laughter and excitability) have mutations in the ''MECP2'' gene. Lastly, ''MECP2'' mutations or changes in the gene's activity have been reported in some cases of [[autism]] (a developmental disorder that affects communication and social interaction).<ref>{{cite news |last=Hunt |first=Katie |url=http://www.cnn.com/2016/01/27/asia/china-autism-monkeys/index.html |title=Chinese scientists create monkeys with autism gene |work=CNN News |date=12 January 2016 |accessdate=27 January 2016}}</ref>

More recent studies reported genetic polymorphisms in the MeCP2 gene in patients with [[systemic lupus erythematosus]] (SLE).<ref name="pmid18320046">{{cite journal | vauthors = Sawalha AH, Webb R, Han S, Kelly JA, Kaufman KM, Kimberly RP, Alarcón-Riquelme ME, James JA, Vyse TJ, Gilkeson GS, Choi CB, Scofield RH, Bae SC, Nath SK, Harley JB | editor1-last = Jin | editor1-first = Dong-Yan | title = Common variants within MECP2 confer risk of systemic lupus erythematosus | journal = PLOS ONE | volume = 3 | issue = 3 | pages = e1727 | year = 2008 | pmid = 18320046 | pmc = 2253825 | doi = 10.1371/journal.pone.0001727 | bibcode = 2008PLoSO...3.1727S | doi-access = free }} {{open access}}</ref> SLE is a systemic autoimmune disease that can affect multiple organs. MeCP2 polymorphisms have been reported so far in European-derived and Asian lupus patients.

The genetic loss of MECP2 has been identified as changing the properties of cells in the [[locus ceruleus]], the exclusive source of noradrenergic innervation to the [[cerebral cortex]] and [[hippocampus]].<ref name="Taneja">{{cite journal |vauthors=Taneja P, Ogier M, Brooks-Harris G, Schmid DA, Katz DM, Nelson SB | year = 2009 | title = Pathophysiology of Locus Ceruleus Neurons in a Mouse Model of Rett Syndrome | journal = Journal of Neuroscience | pmid = 19793977 | volume = 29 | issue = 39 | pmc = 2846656| pages = 12187–12195 | doi = 10.1523/JNEUROSCI.3156-09.2009 }}</ref>

Researchers have concluded that "Because these neurons are a pivotal source of norepinephrine throughout the brainstem and forebrain and are involved in the regulation of diverse functions disrupted in Rett syndrome, such as respiration and cognition, we hypothesize that the locus ceruleus is a critical site at which loss of MECP2 results in CNS dysfunction."<ref name="Taneja"/>

== Interactive pathway map ==
{{MECP2andAssociatedRettSyndrome_WP3584|highlight=MECP2}}

== Interactions ==

MECP2 has been shown to [[Protein-protein interaction|interact]] with [[SKI protein]]<ref name="pmid11441023">{{cite journal |vauthors=Kokura K, Kaul SC, Wadhwa R, Nomura T, Khan MM, Shinagawa T, Yasukawa T, Colmenares C, Ishii S | title = The Ski protein family is required for MeCP2-mediated transcriptional repression | journal = J. Biol. Chem. | volume = 276 | issue = 36 | pages = 34115–21 |date=September 2001 | pmid = 11441023 | doi = 10.1074/jbc.M105747200 | doi-access = free }}</ref> and [[Nuclear receptor co-repressor 1]].<ref name=pmid11441023/>  In neuronal cells the MECP2 mRNA is thought to interact with [[Mir-132 microRNA|miR-132]], which silences the expression of the protein.  This forms part of a homeostatic mechanism that could regulate MECP2 levels in the brain.<ref name="pmid17994015">{{cite journal |vauthors=Klein ME, Lioy DT, Ma L, Impey S, Mandel G, Goodman RH | title = Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA | journal = Nat. Neurosci. | volume = 10 | issue = 12 | pages = 1513–4 |date=December 2007 | pmid = 17994015 | doi = 10.1038/nn2010 | s2cid = 29308441 }}</ref>

== MeCP2 and hormones ==
MeCP2 in the developing rat brain regulates important social development in a sexually dimorphic manner. MeCP2 levels are different between males and females in the developing rat brain 24 hours after birth within the [[amygdala]] and [[hypothalamus]], but this difference is no longer observed 10 days after birth. Specifically, males express less MeCP2 than females,<ref name="pmid17965589">{{cite journal |vauthors=Kurian JR, Forbes-Lorman RM, Auger AP | title = Sex difference in mecp2 expression during a critical period of rat brain development | journal = Epigenetics | volume = 2 | issue = 3 | pages = 173–8 |date=September 2007 | pmid = 17965589 | doi = 10.4161/epi.2.3.4841 | doi-access = free }}</ref> and this aligns with the steroid-sensitive time period of the neonatal rat brain. Reductions in MeCP2 with [[Small interfering RNA]] (siRNA) during the first few days of life reduce male levels of juvenile social play behavior to female typical levels, but do not affect female juvenile play behavior.<ref name="pmid18614683">{{cite journal |vauthors=Kurian JR, Bychowski ME, Forbes-Lorman RM, Auger CJ, Auger AP | title = Mecp2 organizes juvenile social behavior in a sex-specific manner | journal = J. Neurosci. | volume = 28 | issue = 28 | pages = 7137–42 |date=July 2008 | pmid = 18614683 | pmc = 2569867 | doi = 10.1523/JNEUROSCI.1345-08.2008 }}</ref>

MeCP2 is important in organizing hormone-related behaviors and sex differences in the developing rat amygdala. MeCP2 appears to regulate [[arginine vasopressin]] (AVP) and [[androgen receptor]] (AR) production in male rats but not in females. Vasopressin is known to regulate many social behaviors including pair bonding<ref name="pmid8413608">{{cite journal |vauthors=Winslow JT, Hastings N, Carter CS, Harbaugh CR, Insel TR | title = A role for central vasopressin in pair bonding in monogamous prairie voles | journal = Nature | volume = 365 | issue = 6446 | pages = 545–8 |date=October 1993 | pmid = 8413608 | doi = 10.1038/365545a0 | bibcode = 1993Natur.365..545W | s2cid = 4333114 }}</ref> and social recognition.<ref name="pmid14647484">{{cite journal |vauthors=Bielsky IF, Hu SB, Szegda KL, Westphal H, Young LJ | title = Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice | journal = Neuropsychopharmacology | volume = 29 | issue = 3 | pages = 483–93 |date=March 2004 | pmid = 14647484 | doi = 10.1038/sj.npp.1300360 | doi-access = free }}</ref> While male rats typically have higher levels of vasopressin in the amygdala,<ref name="pmid16310321">{{cite journal |vauthors=De Vries GJ, Panzica GC | title = Sexual differentiation of central vasopressin and vasotocin systems in vertebrates: different mechanisms, similar endpoints | journal = Neuroscience | volume = 138 | issue = 3 | pages = 947–55 | year = 2006 | pmid = 16310321 | pmc = 1457099 | doi = 10.1016/j.neuroscience.2005.07.050 }}</ref> MeCP2 reduction during the first 3 days of life causes a lasting reduction of vasopressin to female typical levels in this brain region that lasted through adulthood. Male rats with reduced MeCP2 levels also show a significant reduction of AR at two weeks following infusion, but this effect is gone by adulthood.<ref name="pmid22430799">{{cite journal |vauthors=Forbes-Lorman RM, Rautio JJ, Kurian JR, Auger AP, Auger CJ | title = Neonatal MeCP2 is important for the organization of sex differences in vasopressin expression | journal = Epigenetics | volume = 7 | issue = 3 | pages = 230–8 |date=March 2012 | pmid = 22430799 | pmc = 3335947 | doi = 10.4161/epi.7.3.19265 }}</ref>

== Early life stress ==

MeCP2 monitors the response to early life stress. Early life stress is correlated with hyper-phosphorylation of the MeCP2 protein in [[paraventricular nucleus]] of the hypothalamus.<ref name="pmid19898468">{{cite journal |vauthors=Murgatroyd C, Patchev AV, Wu Y, Micale V, Bockmühl Y, Fischer D, Holsboer F, Wotjak CT, Almeida OF, Spengler D | title = Dynamic DNA methylation programs persistent adverse effects of early-life stress | journal = Nat. Neurosci. | volume = 12 | issue = 12 | pages = 1559–66 |date=December 2009 | pmid = 19898468 | doi = 10.1038/nn.2436 | s2cid = 3328884 }}</ref> This thus causes a reduced occupancy of MeCP2 at the AVP gene's promoter region, and therefore elevated levels of AVP. Vasopressin is a primary hormone involved in the Hypothalmic-Pituitary-Adrenal Axis, the connectivity in the brain that regulates processing of and reaction to stress. Decreased functioning of the MeCP2 protein thus upregulates the neuronal stress response.

== References ==
{{Reflist|2}}

== Further reading ==
{{Refbegin | 2}}
* {{cite journal |vauthors=Chahrour M, Zoghbi HY |title=The story of Rett syndrome: from clinic to neurobiology |journal=Neuron |year=2007 |pages=422–37 |volume=56 |issue=3  |pmid=17988628 |doi=10.1016/j.neuron.2007.10.001|s2cid=16266882 |doi-access=free }}
* {{cite journal |vauthors=Carney RM, Wolpert CM, Ravan SA, Shahbazian M, Ashley-Koch A, Cuccaro ML, Vance JM, Pericak-Vance MA |title=Identification of MeCP2 mutations in a series of females with autistic disorder |journal=Pediatr Neurol |year=2003 |pages=205–11 |volume=28 |issue=3  |pmid=12770674 |doi=10.1016/S0887-8994(02)00624-0}}
* {{cite journal |vauthors=Kerr AM, Ravine D |title=Review article: breaking new ground with Rett syndrome |journal=J Intellect Disabil Res |year=2003 |pages=580–7 |volume=47 |issue=Pt 8  |pmid=14641805 |doi=10.1046/j.1365-2788.2003.00506.x|doi-access=free }}
* {{cite journal |vauthors=Neul JL, Zoghbi HY |title=Rett syndrome: a prototypical neurodevelopmental disorder |journal=Neuroscientist |year=2004 |pages=118–28 |volume=10 |issue=2  |pmid=15070486 |doi=10.1177/1073858403260995|s2cid=9617631 }}
* {{cite journal |vauthors=Schanen C, Houwink EJ, Dorrani N, Lane J, Everett R, Feng A, Cantor RM, Percy A |title=Phenotypic manifestations of MECP2 mutations in classical and atypical Rett syndrome |journal=Am J Med Genet A |year=2004 |pages=129–40 |volume=126 |issue=2  |pmid=15057977 |doi=10.1002/ajmg.a.20571|s2cid=32897044 }}
* {{cite journal |vauthors=Van den Veyver IB, Zoghbi HY |title=Mutations in the gene encoding methyl-CpG-binding protein 2 cause Rett syndrome |journal=Brain Dev |year=2001 |pages=S147–51 |volume=23 |issue=Suppl 1 |pmid=11738862 |doi=10.1016/S0387-7604(01)00376-X|s2cid=26138178 }}
* {{cite journal |vauthors=Webb T, Latif F |title=Rett syndrome and the MECP2 gene |journal=J Med Genet |year=2001 |pages=217–23 |volume=38 |issue=4  |pmid=11283201 |doi=10.1136/jmg.38.4.217 |pmc=1734858}}
*{{cite journal  |vauthors=Shahbazian MD, Zoghbi HY |title=Rett syndrome and MeCP2: linking epigenetics and neuronal function. |journal=Am. J. Hum. Genet. |volume=71 |issue=6 |pages=1259–72 |year=2003 |pmid=12442230 |doi=10.1086/345360  |pmc=378559  }}
*{{cite journal   |vauthors=Moog U, Smeets EE, van Roozendaal KE, etal |title=Neurodevelopmental disorders in males related to the gene causing Rett syndrome in females (MECP2). |journal=Eur. J. Paediatr. Neurol. |volume=7 |issue=1 |pages=5–12 |year=2003 |pmid=12615169 |doi=10.1016/S1090-3798(02)00134-4  }}
*{{cite journal  |vauthors=Miltenberger-Miltenyi G, Laccone F |title=Mutations and polymorphisms in the human methyl CpG-binding protein MECP2. |journal=Hum. Mutat. |volume=22 |issue=2 |pages=107–15 |year=2004 |pmid=12872250 |doi=10.1002/humu.10243 |s2cid=42516576 |doi-access=free }}
*{{cite journal  |vauthors=Weaving LS, Ellaway CJ, Gécz J, Christodoulou J |title=Rett syndrome: clinical review and genetic update. |journal=J. Med. Genet. |volume=42 |issue=1 |pages=1–7 |year=2006 |pmid=15635068 |doi=10.1136/jmg.2004.027730  |pmc=1735910 }}
*{{cite journal  |vauthors=Bapat S, Galande S |title=Association by guilt: identification of DLX5 as a target for MeCP2 provides a molecular link between genomic imprinting and Rett syndrome. |journal=BioEssays |volume=27 |issue=7 |pages=676–80 |year=2005 |pmid=15954098 |doi=10.1002/bies.20266 }}
*{{cite journal  |author=Zlatanova J |title=MeCP2: the chromatin connection and beyond. |journal=Biochem. Cell Biol. |volume=83 |issue=3 |pages=251–62 |year=2005 |pmid=15959553 |doi=10.1139/o05-048 }}
*{{cite journal  |vauthors=Kaufmann WE, Johnston MV, Blue ME |title=MeCP2 expression and function during brain development: implications for Rett syndrome's pathogenesis and clinical evolution. |journal=Brain Dev. |volume=27 |issue=Suppl 1 |pages=S77–S87 |year=2006 |pmid=16182491 |doi=10.1016/j.braindev.2004.10.008 |s2cid=702975 }}
*{{cite journal  |author=Armstrong DD |title=Can we relate MeCP2 deficiency to the structural and chemical abnormalities in the Rett brain? |journal=Brain Dev. |volume=27 |issue=Suppl 1 |pages=S72–S76 |year=2006 |pmid=16182497 |doi=10.1016/j.braindev.2004.10.009 |s2cid=45587850 }}
*{{cite journal  |vauthors=Santos M, Coelho PA, Maciel P |title=Chromatin remodeling and neuronal function: exciting links. |journal=[[Genes, Brain and Behavior]] |volume=5 |issue=Suppl 2 |pages=80–91 |year=2006 |pmid=16681803 |doi=10.1111/j.1601-183X.2006.00227.x |doi-access=free |hdl=1822/67940 |hdl-access=free }}
*{{cite journal  |vauthors=Bienvenu T, Chelly J |title=Molecular genetics of Rett syndrome: when DNA methylation goes unrecognized. |journal=Nature Reviews Genetics  |volume=7 |issue=6 |pages=415–26 |year=2006 |pmid=16708070 |doi=10.1038/nrg1878 |s2cid=28215286 }}
*{{cite journal  |author=Francke U |title=Mechanisms of disease: neurogenetics of MeCP2 deficiency. |journal=Nature Clinical Practice Neurology |volume=2 |issue=4 |pages=212–21 |year=2007 |pmid=16932552 |doi=10.1038/ncpneuro0148 |s2cid=22710951 }}
{{Refend}}

==External links==
* [https://www.rettsyndrome.org/ International Rett Syndrome Foundation]
* [http://www.rettuk.org/ Rett UK Support and Research Charity] 
* [http://www.reverserett.org.uk/ Reverse Rett UK]
* [http://rettregistry.uk Rett Registry UK]
* [http://www.rsrt.org/ Rett Syndrome Research Trust]
* {{Ensembl|ENSG00000169057|ENSP00000301948}}
* [https://www.genecards.org/cgi-bin/carddisp?MECP2 GeneCard]
* [http://mecp2.chw.edu.au/ RettBASE: IRSA MECP2 Variation Database]
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=rett GeneReview/NIH/UW entry on MECP2-Related Disorders]
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=mecp2-dup GeneReviews/NCBI/NIH/UW entry on MECP2 Duplication Syndrome]
* [https://web.archive.org/web/20130517231758/http://www.mecp2.co.uk/ UK Site for Families Affected by MECP2.]
* [https://web.archive.org/web/20100206220126/http://www.mecp2duplication.com/cms/ Site for Families Affected by MECP2.]
* [http://www.duplication-mecp2.fr/ Site officiel français sur la duplication MeCP2]

{{PDB Gallery|geneid=4204}}
{{Authority control}}

[[Category:DNA-binding proteins]]
[[Category:Transcription factors]]
[[Category:Genes on human chromosome X]]