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A common genetic cause of CHD is the 22q11.2 deletion, which is the basis of the homonymous deletion syndrome (22q11.2DS), also known as DiGeorge syndrome. Most of its clinical spectrum is caused by haploinsufficiency of<jats:italic>Tbx1<\/jats:italic>, a gene encoding a T-box transcription factor. Here we show that Tbx1 positively regulates monomethylation of histone 3 lysine 4 (H3K4me1) through interaction with and recruitment of histone methyltransferases. Treatment of cells with tranylcypromine (TCP), an inhibitor of histone demethylases, rebalances the loss of H3K4me1 and rescues the expression of approximately one-third of the genes dysregulated by<jats:italic>Tbx1<\/jats:italic>suppression. In Tbx1 mouse mutants, TCP treatment ameliorates substantially the cardiovascular phenotype. These data suggest that epigenetic drugs may represent a potential therapeutic strategy for rescue of gene haploinsufficiency phenotypes, including structural defects.<\/jats:p>","DOI":"10.1038\/ncomms11688","type":"journal-article","created":{"date-parts":[[2016,6,3]],"date-time":"2016-06-03T11:03:34Z","timestamp":1464951814000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Rebalancing gene haploinsufficiency in vivo by targeting chromatin"],"prefix":"10.1038","volume":"7","author":[{"given":"Filomena Gabriella","family":"Fulcoli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Franzese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Angelini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5330-0256","authenticated-orcid":false,"given":"Antonio","family":"Baldini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,3]]},"reference":[{"key":"BFncomms11688_CR1","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1038\/85845","volume":"27","author":"LA Jerome","year":"2001","unstructured":"Jerome, L. 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