{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:36:52Z","timestamp":1760060212390,"version":"build-2065373602"},"reference-count":64,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education","award":["No. 122020300041-7"],"award-info":[{"award-number":["No. 122020300041-7"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epigenomes"],"abstract":"<jats:p>Background. Studies of comorbid (syntropic) and inversely comorbid (rarely occurring together, i.e., dystropic) diseases have focused on the search for molecular causes of this phenomenon. Materials. We investigated DNA methylation levels in regulatory regions of 23 apoptosis-associated genes as candidate loci associated with the \u201ccancer\u2013neurodegeneration\u201d dystropy in patients with Huntington\u2019s disease (HD) and patients with non\u2013small cell lung cancer (LC). Results. Statistically significant differences in methylation levels between the HD and LC groups were found for 41 CpG sites in 16 genes. The results show that five genes (SETDB1, TWIST1, HDAC1, SP1, and GRIA2) are probably involved in the phenomenon of inverse comorbidity of these diseases. For these genes, the methylation levels of the studied CpG sites were altered in opposite directions in the two groups of patients, compared to the control group. Conclusions. For the SP1 gene, the above hypothesis is supported by our analysis of open-access data on gene expression in patients with the aforementioned diagnoses and fits a probable mechanism of the \u201cHD\u2013LC\u201d dystropy.<\/jats:p>","DOI":"10.3390\/epigenomes9030028","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T10:58:26Z","timestamp":1754564306000},"page":"28","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DNA Methylation Status of Regulatory Regions of Apoptosis-Associated Genes in Dystropy \u00abHuntington\u2019s Disease\u2014Non-Small Cell Lung Cancer\u00bb"],"prefix":"10.3390","volume":"9","author":[{"given":"Nadezhda P.","family":"Babushkina","sequence":"first","affiliation":[{"name":"Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 10 Ushayka Embankment, Tomsk 634050, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena Yu.","family":"Bragina","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 10 Ushayka Embankment, Tomsk 634050, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7882-2093","authenticated-orcid":false,"given":"Densema E.","family":"Gomboeva","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 10 Ushayka Embankment, Tomsk 634050, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1498-6934","authenticated-orcid":false,"given":"Iuliia A.","family":"Koroleva","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 10 Ushayka Embankment, Tomsk 634050, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2704-6282","authenticated-orcid":false,"given":"Sergey N.","family":"Illarioshkin","sequence":"additional","affiliation":[{"name":"Research Center of Neurology, 80 Volokolamskoye Shosse, Moscow 125367, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8752-7045","authenticated-orcid":false,"given":"Sergey A.","family":"Klyushnikov","sequence":"additional","affiliation":[{"name":"Research Center of Neurology, 80 Volokolamskoye Shosse, Moscow 125367, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9419-1159","authenticated-orcid":false,"given":"Nataliya Yu.","family":"Abramycheva","sequence":"additional","affiliation":[{"name":"Research Center of Neurology, 80 Volokolamskoye Shosse, Moscow 125367, 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K.","family":"Ibragimova","sequence":"additional","affiliation":[{"name":"Tomsk Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 5 Kooperativny Street, Tomsk 634009, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7419-4512","authenticated-orcid":false,"given":"Matvey M.","family":"Tsyganov","sequence":"additional","affiliation":[{"name":"Tomsk Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 5 Kooperativny Street, Tomsk 634009, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2716-3075","authenticated-orcid":false,"given":"Irina A.","family":"Tsydenova","sequence":"additional","affiliation":[{"name":"Tomsk Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 5 Kooperativny Street, Tomsk 634009, 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J. Genet."},{"key":"ref_2","first-page":"297","article-title":"Genetic outline of the hermeneutics of the diseases connection phenomenon in human","volume":"27","author":"Bragina","year":"2023","journal-title":"Vavilov J. Genet. Breed."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1159\/000356498","article-title":"Inverse and direct cancer comorbidity in people with central nervous system disorders: A meta-analysis of cancer incidence in 577,013 participants of 50 observational studies","volume":"83","author":"Valderas","year":"2014","journal-title":"Psychother. Psychosom."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"For\u00e9s-Martos, J., Boullosa, C., Rodrigo-Dom\u00ednguez, D., S\u00e1nchez-Valle, J., Suay-Garc\u00eda, B., Climent, J., Falc\u00f3, A., Valencia, A., Puig-Butill\u00e9, J.A., and Puig, S. (2021). Transcriptomic and Genetic Associations between Alzheimer\u2019s Disease, Parkinson\u2019s Disease, and Cancer. Cancers, 13.","DOI":"10.3390\/cancers13122990"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7627","DOI":"10.1007\/s11033-021-06723-0","article-title":"A study of gene expression by RNA-seq in patients with prostate cancer and in patients with Parkinson disease: An example of inverse comorbidity","volume":"48","author":"Pepe","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1134\/S1022795420030059","article-title":"The inverse comorbidity between oncological diseases and huntington\u2019s disease: Review of epidemiological and biological evidence","volume":"56","author":"Gomboeva","year":"2020","journal-title":"Russ. J. Genet."},{"key":"ref_7","unstructured":"(2024, January 10). Online Catalog of Human Genes and Genetic Disorders (OMIM). Available online: https:\/\/www.omim.org."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.1523\/JNEUROSCI.20-10-03705.2000","article-title":"Wild-type huntingtin protects from apoptosis upstream of caspase-3","volume":"20","author":"Rigamonti","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"216662","DOI":"10.1016\/j.canlet.2024.216662","article-title":"The interplay between autophagy and apoptosis: Its implication in lung cancer and therapeutics","volume":"585","author":"Biswas","year":"2024","journal-title":"Cancer Lett."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bragina, E.Y., Gomboeva, D.E., Saik, O.V., Ivanisenko, V.A., Freidin, M.B., Nazarenko, M.S., and Puzyrev, V.P. (2023). Apoptosis Genes as a Key to Identification of Inverse Comorbidity of Huntington\u2019s Disease and Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119385"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Salameh, Y., Bejaoui, Y., and El Hajj, N. (2020). DNA Methylation Biomarkers in Aging and Age-Related Diseases. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00171"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zsindely, N., Si\u00e1gi, F., and Bodai, L. (2021). DNA Methylation in Huntington\u2019s Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222312736"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13148-023-01464-2","article-title":"Healthy lifestyle, DNA methylation age acceleration, and incident risk of coronary heart disease","volume":"15","author":"Si","year":"2023","journal-title":"Clin. Epigenetics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"617","DOI":"10.18632\/aging.204501","article-title":"Epigenetic age and lung cancer risk in the CLUE II prospective cohort study","volume":"15","author":"Michaud","year":"2023","journal-title":"Aging"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1136\/jnnp-2022-330931","article-title":"Epigenetic clocks in neurodegenerative diseases: A systematic review","volume":"94","author":"Yang","year":"2023","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_16","unstructured":"(2023, January 20). Eukaryotic Promotor Database (EPD). Available online: https:\/\/epd.expasy.org\/epd."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1146\/annurev-psych-122414-033653","article-title":"Principles and Challenges of Applying Epigenetic Epidemiology to Psychology","volume":"69","author":"Jones","year":"2018","journal-title":"Annu. Rev. Psychol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s13148-015-0148-3","article-title":"DNA methylation changes of whole blood cells in response to active smoking exposure in adults: A systematic review of DNA methylation studies","volume":"7","author":"Gao","year":"2015","journal-title":"Clin. Epigenet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.ajhg.2016.02.019","article-title":"DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis","volume":"98","author":"Joubert","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1289\/EHP595","article-title":"Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children\u2019s Environmental Health Studies: The Children\u2019s Environmental Health and Disease Prevention Research Center\u2019s Epigenetics Working Group","volume":"125","author":"Breton","year":"2017","journal-title":"Environ. Health Perspect."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1186\/s12967-022-03662-7","article-title":"Genetic and epigenetic regulation of Catechol-O-methyltransferase in relation to inflammation in chronic fatigue syndrome and Fibromyalgia","volume":"20","author":"Polli","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_22","unstructured":"(2024, March 15). UCSC Genome Browser. Available online: https:\/\/genome.ucsc.edu."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"D126","DOI":"10.1093\/nar\/gkv1203","article-title":"ORegAnno 3.0: A community-driven resource for curated regulatory annotation","volume":"44","author":"Lesurf","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_24","unstructured":"(2024, March 02). ENCODE. Available online: https:\/\/www.encodeproject.org\/."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"ENCODE Project Consortium, Moore, J.E., Purcaro, M.J., Pratt, H.E., Epstein, C.B., Shoresh, N., Adrian, J., Kawli, T., Davis, C.A., and Dobin, A. (2020). Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature, 583, 699\u2013710.","DOI":"10.1038\/s41586-020-2493-4"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1021\/bi0611208","article-title":"Solution structure of human Brg1 bromodomain and its specific binding to acetylated histone tails","volume":"46","author":"Shen","year":"2007","journal-title":"Biochemistry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1016\/j.febslet.2015.05.022","article-title":"Structural impact of complete CpG methylation within target DNA on specific complex formation of the inducible transcription factor Egr-1","volume":"589","author":"Zandarashvili","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/s10038-021-00931-z","article-title":"RBL2 bi-allelic truncating variants cause severe motor and cognitive impairment without evidence for abnormalities in DNA methylation or telomeric function","volume":"66","author":"Samra","year":"2021","journal-title":"J. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4059","DOI":"10.1182\/blood.V93.12.4059","article-title":"DNA methylation","volume":"93","author":"Singal","year":"1999","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3672","DOI":"10.1158\/1078-0432.CCR-08-2343","article-title":"Interaction of TFAP2C with the estrogen receptor-\u03b1 promoter is controlled by chromatin structure","volume":"15","author":"Woodfield","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1093\/nar\/gkt1236","article-title":"Establishment of active chromatin structure at enhancer elements by mixed-lineage leukemia 1 to initiate estrogen-dependent gene expression","volume":"42","author":"Jeong","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Le Berre, G., Hossard, V., Riou, J.F., and Guieysse-Peugeot, A.L. (2019). Repression of TERRA Expression by Subtelomeric DNA Methylation Is Dependent on NRF1 Binding. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112791"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Pepin, M.E., Infante, T., Benincasa, G., Schiano, C., Miceli, M., Ceccarelli, S., Megiorni, F., Anastasiadou, E., Della Valle, G., and Fatone, G. (2020). Differential DNA Methylation Encodes Proliferation and Senescence Programs in Human Adipose-Derived Mesenchymal Stem Cells. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00346"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13073-021-00880-4","article-title":"Crosstalk between microRNA expression and DNA methylation drives the hormone-dependent phenotype of breast cancer","volume":"13","author":"Aure","year":"2021","journal-title":"Genome Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3892\/mmr.2022.12609","article-title":"CpG site hypomethylation at ETS1-binding region regulates DLK1 expression in Chinese patients with Tetralogy of Fallot","volume":"25","author":"Tian","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.1038\/onc.2012.400","article-title":"Transcriptional regulation of the GPX1 gene by TFAP2C and aberrant CpG methylation in human breast cancer","volume":"32","author":"Kulak","year":"2013","journal-title":"Oncogene"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1093\/nar\/gkt1323","article-title":"c-Jun\/c-Fos heterodimers regulate cellular genes via a newly identified class of methylated DNA sequence motifs","volume":"42","author":"Gustems","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4905","DOI":"10.1093\/emboj\/17.17.4905","article-title":"CpG methylation, chromatin structure and gene silencing\u2014A three-way connection","volume":"17","author":"Razin","year":"1998","journal-title":"EMBO J."},{"key":"ref_39","unstructured":"(2024, January 17). Genotype-Tissue Expression (GTEx) Portal. Available online: https:\/\/www.gtexportal.org\/home."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7120","DOI":"10.1038\/sj.onc.1204891","article-title":"Methylation in hMLH1 promoter interferes with its binding to transcription factor CBF and inhibits gene expression","volume":"20","author":"Deng","year":"2001","journal-title":"Oncogene"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.jmoldx.2019.11.005","article-title":"Reliable Clinical MLH1 Promoter Hypermethylation Assessment Using a High-Throughput Genome-Wide Methylation Array Platform","volume":"22","author":"Benhamida","year":"2020","journal-title":"J. Mol. Diagn."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1073\/pnas.0906183107","article-title":"Evolution in health and medicine Sackler colloquium: Stochastic epigenetic variation as a driving force of development, evolutionary adaptation, and disease","volume":"107","author":"Feinberg","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.ajhg.2013.10.004","article-title":"Global analysis of DNA methylation variation in adipose tissue from twins reveals links to disease-associated variants in distal regulatory elements","volume":"93","author":"Grundberg","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ahsan, M., Ek, W.E., Rask-Andersen, M., Karlsson, T., Lind-Thomsen, A., Enroth, S., Gyllensten, U., and Johansson, \u00c5. (2017). The relative contribution of DNA methylation and genetic variants on protein biomarkers for human diseases. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1007005"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1515\/bmc-2014-0039","article-title":"Epigenetic considerations of the APOE gene","volume":"6","author":"Yu","year":"2015","journal-title":"Biomol. Concepts"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"745","DOI":"10.3233\/JAD-143060","article-title":"The APOE Gene is Differentially Methylated in Alzheimer\u2019s Disease","volume":"48","author":"Foraker","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_47","first-page":"P1308","article-title":"APOE RNA production is modulated by dna methylation near \u03b52\/\u03b53\/\u03b54 defining SNPs","volume":"15","author":"Yu","year":"2019","journal-title":"Alzheimer\u2019s Dement. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1134\/S0026893323040027","article-title":"Methylation of Regulatory Regions of DNA Repair Genes in Carotid Atherosclerosis","volume":"57","author":"Babushkina","year":"2023","journal-title":"Mol. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/nn.4014","article-title":"A SNP in the HTT promoter alters NF-\u03baB binding and is a bidirectional genetic modifier of Huntington disease","volume":"18","author":"Neal","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.gene.2015.12.050","article-title":"Polymorphisms in mismatch repair genes are associated with risk and microsatellite instability of gastric cancer, and interact with life exposures","volume":"579","author":"Zhu","year":"2016","journal-title":"Gene"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1080\/15592294.2017.1305527","article-title":"Modulation of transcription factor binding and epigenetic regulation of the MLH1 CpG island and shore by polymorphism rs1800734 in colorectal cancer","volume":"12","author":"Savio","year":"2017","journal-title":"Epigenetics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"80039","DOI":"10.18632\/oncotarget.16899","article-title":"Single nucleotide polymorphisms in MLH1 predict poor prognosis of hepatocellular carcinoma in a Chinese population","volume":"8","author":"Zhu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Thomas, R., Trapani, D., Goodyer-Sait, L., Tomkova, M., Fernandez-Rozadilla, C., Sahnane, N., Woolley, C., Davis, H., Chegwidden, L., and Kriaucionis, S. (2019). The polymorphic variant rs1800734 influences methylation acquisition and allele-specific TFAP4 binding in the MLH1 promoter leading to differential mRNA expression. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-49952-x"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.31557\/APJCP.2023.24.8.2911","article-title":"MLH1 rs1800734 Pathogenic Variant among Patients with Colorectal Cancer in the Lower Northeastern Region of Thailand","volume":"24","author":"Pongsavee","year":"2023","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Savio, A.J., Lemire, M., Mrkonjic, M., Gallinger, S., Zanke, B.W., Hudson, T.J., and Bapat, B. (2012). MLH1 region polymorphisms show a significant association with CpG island shore methylation in a large cohort of healthy individuals. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051531"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s12031-012-9739-z","article-title":"Sp1 regulates human huntingtin gene expression","volume":"47","author":"Wang","year":"2012","journal-title":"J. Mol. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1126\/science.1072613","article-title":"Sp1 and TAFII130 transcriptional activity disrupted in early Huntington\u2019s disease","volume":"296","author":"Dunah","year":"2002","journal-title":"Science"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2008.03.074","article-title":"Sp1: Emerging roles\u2014Beyond constitutive activation of TATA-less housekeeping genes","volume":"372","author":"Wierstra","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.nbd.2005.11.001","article-title":"Decreased association of the transcription factor Sp1 with genes downregulated in Huntington\u2019s disease","volume":"22","author":"Yohrling","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.nbd.2011.07.001","article-title":"What have we learned from gene expression profiles in Huntington\u2019s disease?","volume":"45","author":"Seredenina","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Conforti, P., Besusso, D., Brocchetti, S., Campus, I., Cappadona, C., Galimberti, M., Laporta, A., Iennaco, R., Rossi, R.L., and Dickinson, V.B. (2020). RUES2 hESCs exhibit MGE-biased neuronal differentiation and muHTT-dependent defective specification hinting at SP1. Neurobiol. Dis., 146.","DOI":"10.1016\/j.nbd.2020.105140"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3973","DOI":"10.1038\/onc.2011.568","article-title":"Sp1 expression regulates lung tumor progression","volume":"31","author":"Hsu","year":"2012","journal-title":"Oncogene"},{"key":"ref_63","first-page":"pdb.prot4455","article-title":"Purification of nucleic acids by extraction with phenol:chloroform","volume":"2006","author":"Sambrook","year":"2006","journal-title":"CSH Protoc."},{"key":"ref_64","first-page":"52488","article-title":"Targeted DNA methylation analysis by next-generation sequencing","volume":"96","author":"Masser","year":"2015","journal-title":"J. Vis. 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