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000140109 1001_ $$0P:(DE-HGF)0$$aWeber, Axel$$b0$$eCorresponding author
000140109 245__ $$aEpigenome-wide DNA methylation profiling in Progressive Supranuclear Palsy reveals major changes at DLX1.
000140109 260__ $$a[London]$$bNature Publishing Group UK$$c2018
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000140109 520__ $$aGenetic, epigenetic, and environmental factors contribute to the multifactorial disorder progressive supranuclear palsy (PSP). Here, we study epigenetic changes by genome-wide analysis of DNA from postmortem tissue of forebrains of patients and controls and detect significant (P < 0.05) methylation differences at 717 CpG sites in PSP vs. controls. Four-hundred fifty-one of these sites are associated with protein-coding genes. While differential methylation only affects a few sites in most genes, DLX1 is hypermethylated at multiple sites. Expression of an antisense transcript of DLX1, DLX1AS, is reduced in PSP brains. The amount of DLX1 protein is increased in gray matter of PSP forebrains. Pathway analysis suggests that DLX1 influences MAPT-encoded Tau protein. In a cell system, overexpression of DLX1 results in downregulation of MAPT while overexpression of DLX1AS causes upregulation of MAPT. Our observations suggest that altered DLX1 methylation and expression contribute to pathogenesis of PSP by influencing MAPT.
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000140109 650_7 $$2NLM Chemicals$$aDistal-less homeobox proteins
000140109 650_7 $$2NLM Chemicals$$aHomeodomain Proteins
000140109 650_7 $$2NLM Chemicals$$aMAPT protein, human
000140109 650_7 $$2NLM Chemicals$$aTranscription Factors
000140109 650_7 $$2NLM Chemicals$$atau Proteins
000140109 650_2 $$2MeSH$$aAged
000140109 650_2 $$2MeSH$$aAged, 80 and over
000140109 650_2 $$2MeSH$$aDNA Methylation: genetics
000140109 650_2 $$2MeSH$$aEpigenesis, Genetic: genetics
000140109 650_2 $$2MeSH$$aFemale
000140109 650_2 $$2MeSH$$aHomeodomain Proteins: genetics
000140109 650_2 $$2MeSH$$aHomeodomain Proteins: metabolism
000140109 650_2 $$2MeSH$$aHumans
000140109 650_2 $$2MeSH$$aMale
000140109 650_2 $$2MeSH$$aSupranuclear Palsy, Progressive: genetics
000140109 650_2 $$2MeSH$$aSupranuclear Palsy, Progressive: pathology
000140109 650_2 $$2MeSH$$aTranscription Factors: genetics
000140109 650_2 $$2MeSH$$aTranscription Factors: metabolism
000140109 650_2 $$2MeSH$$atau Proteins: genetics
000140109 650_2 $$2MeSH$$atau Proteins: metabolism
000140109 7001_ $$0P:(DE-2719)2812262$$aSchwarz, Sigrid C$$b1$$udzne
000140109 7001_ $$0P:(DE-HGF)0$$aTost, Jörg$$b2
000140109 7001_ $$0P:(DE-HGF)0$$aTrümbach, Dietrich$$b3
000140109 7001_ $$0P:(DE-HGF)0$$aWinter, Pia$$b4
000140109 7001_ $$0P:(DE-HGF)0$$aBusato, Florence$$b5
000140109 7001_ $$0P:(DE-HGF)0$$aTacik, Pawel$$b6
000140109 7001_ $$0P:(DE-HGF)0$$aWindhorst, Anita C$$b7
000140109 7001_ $$0P:(DE-HGF)0$$aFagny, Maud$$b8
000140109 7001_ $$0P:(DE-2719)2811333$$aArzberger, Thomas$$b9$$udzne
000140109 7001_ $$0P:(DE-HGF)0$$aMcLean, Catriona$$b10
000140109 7001_ $$0P:(DE-HGF)0$$avan Swieten, John C$$b11
000140109 7001_ $$0P:(DE-HGF)0$$aSchwarz, Johannes$$b12
000140109 7001_ $$0P:(DE-2719)9000331$$aVogt-Weisenhorn, Daniela$$b13$$udzne
000140109 7001_ $$0P:(DE-2719)2000028$$aWurst, Wolfgang$$b14$$udzne
000140109 7001_ $$0P:(DE-HGF)0$$aAdhikary, Till$$b15
000140109 7001_ $$0P:(DE-HGF)0$$aDickson, Dennis W$$b16
000140109 7001_ $$0P:(DE-2719)2811373$$aHöglinger, Günter U$$b17$$udzne
000140109 7001_ $$0P:(DE-HGF)0$$aMüller, Ulrich$$b18
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000140109 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-018-05325-y$$gVol. 9, no. 1, p. 2929$$n1$$p2929$$q9:1<2929$$tNature Communications$$v9$$x2041-1723$$y2018
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