Promoter-Adjacent DNA Hypermethylation Can Downmodulate Gene Expression: TBX15 in the Muscle Lineage
Abstract
:1. Introduction
2. Results
2.1. Myoblast DNA Hypermethylation around an Unmethylated Promoter Region in Five T-Box Genes Was Positively Associated with Their Expression
2.2. DNA Sequences That Were Part of Myoblast Hypermethylated DMRs near the TBX15 Promoter Region Display Promoter or Enhancer Activity upon Transfection into Myoblasts
2.3. Much Lower Enhancer and Promoter Activity Was Seen for Transfected TBX15 TSS-Upstream or Downstream Sequences in Non-Myoblast vs. Myoblast Host Cells
2.4. Transfection of M.SssI CpG-methylated TBX15 DMRs in Reporter Constructs
2.5. Variable TBX15 Epigenetics in Skeletal Muscle Samples, Myoblast and Skin Fibroblast Cell Strains, Adipocytes, and Cancer Cell Lines
2.6. Transcription Factor Binding Sites in the 5′ TBX15 Region
3. Discussion
4. Materials and Methods
4.1. Preparation of DNA Constructs, Transfection, and In Vitro DNA Methylation
4.2. EM-Seq and WGBS on Myoblast DNA and Determination of DMRs and LMRs
4.3. Bioinformatics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- L’Honore, A.; Drouin, J.; Buckingham, M.; Montarras, D. Pitx2 and Pitx3 transcription factors: Two key regulators of the redox state in adult skeletal muscle stem cells and muscle regeneration. Free Radic. Biol. Med. 2014, 75, S37. [Google Scholar] [CrossRef] [PubMed]
- Singh, M.K.; Petry, M.; Haenig, B.; Lescher, B.; Leitges, M.; Kispert, A. The T-box transcription factor Tbx15 is required for skeletal development. Mech. Dev. 2005, 122, 131–144. [Google Scholar] [CrossRef] [PubMed]
- Papaioannou, V.E. The T-box gene family: Emerging roles in development, stem cells and cancer. Development 2014, 141, 3819–3833. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Arribas, J.; Gimenez, E.; Marcos, R.; Velazquez, A. Novel antiapoptotic effect of TBX15: Overexpression of TBX15 reduces apoptosis in cancer cells. Apoptosis 2015, 20, 1338–1346. [Google Scholar] [CrossRef] [PubMed]
- Pan, D.Z.; Miao, Z.; Comenho, C.; Rajkumar, S.; Koka, A.; Lee, S.H.T.; Alvarez, M.; Kaminska, D.; Ko, A.; Sinsheimer, J.S.; et al. Identification of TBX15 as an adipose master trans regulator of abdominal obesity genes. Genome Med. 2021, 13, 123. [Google Scholar] [CrossRef]
- Lee, K.Y.; Sharma, R.; Gase, G.; Ussar, S.; Li, Y.; Welch, L.; Berryman, D.E.; Kispert, A.; Bluher, M.; Kahn, C.R. Tbx15 defines a glycolytic subpopulation and white adipocyte heterogeneity. Diabetes 2017, 66, 2822–2829. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- de Araujo, T.K.; Secolin, R.; Félix, T.M.; de Souza, L.T.; Fontes, M.; Monlleó, I.L.; de Souza, J.; Fett-Conte, A.C.; Ribeiro, E.M.; Xavier, A.C.; et al. A multicentric association study between 39 genes and nonsyndromic cleft lip and palate in a Brazilian population. J. Craniomaxillofac. Surg. 2016, 44, 16–20. [Google Scholar] [CrossRef] [PubMed]
- Stelzer, G.; Rosen, N.; Plaschkes, I.; Zimmerman, S.; Twik, M.; Fishilevich, S.; Stein, T.I.; Nudel, R.; Lieder, I.; Mazor, Y.; et al. The GeneCards Suite: From gene data mining to disease genome sequence analyses. Curr. Protoc. Bioinform. 2016, 54, 1–30. [Google Scholar] [CrossRef]
- Candille, S.I.; Van Raamsdonk, C.D.; Chen, C.; Kuijper, S.; Chen-Tsai, Y.; Russ, A.; Meijlink, F.; Barsh, G.S. Dorsoventral patterning of the mouse coat by Tbx15. PLoS Biol. 2004, 2, e3. [Google Scholar] [CrossRef]
- Lee, K.Y.; Singh, M.K.; Ussar, S.; Wetzel, P.; Hirshman, M.F.; Goodyear, L.J.; Kispert, A.; Kahn, C.R. Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism. Nat. Commun. 2015, 6, 8054. [Google Scholar] [CrossRef]
- Osborn, D.P.S.; Li, K.; Cutty, S.J.; Nelson, A.C.; Wardle, F.C.; Hinits, Y.; Hughes, S.M. Fgf-driven Tbx protein activities directly induce myf5 and myod to initiate zebrafish myogenesis. Development 2020, 147, dev184689. [Google Scholar] [CrossRef] [PubMed]
- Hubert, J.; Bourgeois, C.A. The nuclear skeleton and the spatial arrangement of chromosomes in the interphase nucleus of vertebrate somatic cells. Hum. Genet. 1986, 74, 1–15. [Google Scholar] [CrossRef] [PubMed]
- Williams, K.; Ingerslev, L.R.; Bork-Jensen, J.; Wohlwend, M.; Hansen, A.N.; Small, L.; Ribel-Madsen, R.; Astrup, A.; Pedersen, O.; Auwerx, J.; et al. Skeletal muscle enhancer interactions identify genes controlling whole-body metabolism. Nat. Commun. 2020, 11, 2695. [Google Scholar] [CrossRef] [PubMed]
- Chandra, S.; Baribault, C.; Lacey, M.; Ehrlich, M. Myogenic differential methylation: Diverse associations with chromatin structure. Biology 2014, 3, 426–451. [Google Scholar] [CrossRef] [Green Version]
- Myers, R.M.; Stamatoyannopoulos, J.; Snyder, M.; Dunham, I.; Hardison, R.C.; Bernstein, B.E.; Gingeras, T.R.; Kent, W.J.; Birney, E.; Wold, B.; et al. A user’s guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol. 2011, 9, e1001046. [Google Scholar]
- Massenet, J.; Gardner, E.; Chazaud, B.; Dilworth, F.J. Epigenetic regulation of satellite cell fate during skeletal muscle regeneration. Skelet. Muscle 2021, 11, 4. [Google Scholar] [CrossRef]
- Zhang, X.; Ehrlich, K.C.; Yu, F.; Hu, X.; Meng, X.H.; Deng, H.W.; Shen, H.; Ehrlich, M. Osteoporosis- and obesity-risk interrelationships: An epigenetic analysis of GWAS-derived SNPs at the developmental gene TBX15. Epigenetics 2020, 15, 728–749. [Google Scholar] [CrossRef] [Green Version]
- Dahlet, T.; Argueso Lleida, A.; Al Adhami, H.; Dumas, M.; Bender, A.; Ngondo, R.P.; Tanguy, M.; Vallet, J.; Auclair, G.; Bardet, A.F.; et al. Genome-wide analysis in the mouse embryo reveals the importance of DNA methylation for transcription integrity. Nat. Commun. 2020, 11, 3153. [Google Scholar] [CrossRef]
- Kundaje, A.; Meuleman, W.; Ernst, J.; Bilenky, M.; Yen, A.; Heravi-Moussavi, A.; Kheradpour, P.; Zhang, Z.; Wang, J.; Ziller, M.J.; et al. Integrative analysis of 111 reference human epigenomes. Nature 2015, 518, 317–330. [Google Scholar] [CrossRef] [Green Version]
- Min, J.L.; Hemani, G.; Hannon, E.; Dekkers, K.F.; Castillo-Fernandez, J.; Luijk, R.; Carnero-Montoro, E.; Lawson, D.J.; Burrows, K.; Suderman, M.; et al. Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation. Nat. Genet. 2021, 53, 1311–1321. [Google Scholar] [CrossRef]
- Song, Q.; Decato, B.; Hong, E.E.; Zhou, M.; Fang, F.; Qu, J.; Garvin, T.; Kessler, M.; Zhou, J.; Smith, A.D. A reference methylome database and analysis pipeline to facilitate integrative and comparative epigenomics. PLoS ONE 2013, 8, e81148. [Google Scholar] [CrossRef] [PubMed]
- Ehrlich, K.C.; Lacey, M.; Ehrlich, M. Epigenetics of skeletal muscle-associated genes in the ASB, LRRC, TMEM, and OSBPL gene families. Epigenomes 2020, 4, 1. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rosenbloom, K.R.; Armstrong, J.; Barber, G.P.; Casper, J.; Clawson, H.; Diekhans, M.; Dreszer, T.R.; Fujita, P.A.; Guruvadoo, L.; Haeussler, M.; et al. The UCSC Genome Browser database: 2015 update. Nucleic Acids Res. 2015, 43, D670–D681. [Google Scholar] [CrossRef] [Green Version]
- Vaisvila, R.; Ponnaluri, V.K.C.; Sun, Z.; Langhorst, B.W.; Saleh, L.; Guan, S.; Dai, N.; Campbell, M.A.; Sexton, B.S.; Marks, K.; et al. Enzymatic methyl sequencing detects DNA methylation at single-base resolution from picograms of DNA. Genome Res. 2021, 31, 1280–1289. [Google Scholar] [CrossRef]
- Niu, G.; Hao, J.; Sheng, S.; Wen, F. Role of T-box genes in cancer, epithelial-mesenchymal transition, and cancer stem cells. J. Cell. Biochem. 2022, 123, 215–230. [Google Scholar] [CrossRef]
- Lee, S.M.; Lee, J.; Noh, K.M.; Choi, W.Y.; Jeon, S.; Oh, G.T.; Kim-Ha, J.; Jin, Y.; Cho, S.W.; Kim, Y.J. Intragenic CpG islands play important roles in bivalent chromatin assembly of developmental genes. Proc. Natl. Acad. Sci. USA 2017, 114, E1885–E1894. [Google Scholar] [CrossRef] [Green Version]
- Lausch, E.; Hermanns, P.; Farin, H.F.; Alanay, Y.; Unger, S.; Nikkel, S.; Steinwender, C.; Scherer, G.; Spranger, J.; Zabel, B.; et al. TBX15 mutations cause craniofacial dysmorphism, hypoplasia of scapula and pelvis, and short stature in Cousin syndrome. Am. J. Hum. Genet. 2008, 83, 649–655. [Google Scholar] [CrossRef] [Green Version]
- Ehrlich, K.C.; Paterson, H.L.; Lacey, M.; Ehrlich, M. DNA hypomethylation in intragenic and intergenic enhancer chromatin of muscle-specific genes usually correlates with their expression. Yale J. Biol. Med. 2016, 89, 441–455. [Google Scholar]
- Klug, M.; Rehli, M. Functional analysis of promoter CpG methylation using a CpG-free luciferase reporter vector. Epigenetics 2006, 1, 127–130. [Google Scholar] [CrossRef] [Green Version]
- Tsumagari, K.; Baribault, C.; Terragni, J.; Varley, K.E.; Gertz, J.; Pradhan, S.; Baddoo, M.; Crain, C.M.; Song, L.; Crawford, G.E.; et al. Early de novo DNA methylation and prolonged demethylation in the muscle lineage. Epigenetics 2013, 8, 317–332. [Google Scholar] [CrossRef] [Green Version]
- Varley, K.E.; Gertz, J.; Bowling, K.M.; Parker, S.L.; Reddy, T.E.; Pauli-Behn, F.; Cross, M.K.; Williams, B.A.; Stamatoyannopoulos, J.A.; Crawford, G.E.; et al. Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res. 2013, 23, 555–567. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Smith, Z.D.; Gu, H.; Bock, C.; Gnirke, A.; Meissner, A. High-throughput bisulfite sequencing in mammalian genomes. Methods 2009, 48, 226–232. [Google Scholar] [CrossRef] [PubMed]
- Hnisz, D.; Abraham, B.J.; Lee, T.I.; Lau, A.; Saint-Andre, V.; Sigova, A.A.; Hoke, H.A.; Young, R.A. Super-enhancers in the control of cell identity and disease. Cell 2013, 155, 934–947. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jiang, Y.; Qian, F.; Bai, X.; Liu, Y.; Wang, Q.; Ai, B.; Han, X.; Shi, S.; Zhang, J.; Li, X.; et al. SEdb: A comprehensive human super-enhancer database. Nucleic Acids Res. 2019, 47, D235–D243. [Google Scholar] [CrossRef]
- The_GTEx_Consortium. Human genomics. The genotype-tissue expression (GTEx) pilot analysis: Multitissue gene regulation in humans. Science 2015, 348, 648–660. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lister, R.; Pelizzola, M.; Kida, Y.S.; Hawkins, R.D.; Nery, J.R.; Hon, G.; Antosiewicz-Bourget, J.; O’Malley, R.; Castanon, R.; Klugman, S.; et al. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 2011, 471, 68–73. [Google Scholar] [CrossRef] [Green Version]
- Bradford, S.T.; Nair, S.S.; Statham, A.L.; van Dijk, S.J.; Peters, T.J.; Anwar, F.; French, H.J.; von Martels, J.Z.H.; Sutcliffe, B.; Maddugoda, M.P.; et al. Methylome and transcriptome maps of human visceral and subcutaneous adipocytes reveal key epigenetic differences at developmental genes. Sci. Rep. 2019, 9, 9511. [Google Scholar] [CrossRef] [Green Version]
- Karlsson, M.; Zhang, C.; Méar, L.; Zhong, W.; Digre, A.; Katona, B.; Sjöstedt, E.; Butler, L.; Odeberg, J.; Dusart, P.; et al. A single-cell type transcriptomics map of human tissues. Sci. Adv. 2021, 7, eabh2169. [Google Scholar] [CrossRef]
- Puig, R.R.; Boddie, P.; Khan, A.; Castro-Mondragon, J.A.; Mathelier, A. UniBind: Maps of high-confidence direct TF-DNA interactions across nine species. BMC Genom. 2021, 22, 482. [Google Scholar] [CrossRef]
- Cao, Y.; Yao, Z.; Sarkar, D.; Lawrence, M.; Sanchez, G.J.; Parker, M.H.; MacQuarrie, K.L.; Davison, J.; Morgan, M.T.; Ruzzo, W.L.; et al. Genome-wide MyoD binding in skeletal muscle cells: A potential for broad cellular reprogramming. Dev. Cell 2010, 18, 662–674. [Google Scholar] [CrossRef] [Green Version]
- Arribas, J.; Cajuso, T.; Rodio, A.; Marcos, R.; Leonardi, A.; Velázquez, A. NF-κB Mediates the Expression of TBX15 in Cancer Cells. PLoS ONE 2016, 11, e0157761. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Castro-Mondragon, J.A.; Riudavets-Puig, R.; Rauluseviciute, I.; Lemma, R.B.; Turchi, L.; Blanc-Mathieu, R.; Lucas, J.; Boddie, P.; Khan, A.; Manosalva Pérez, N.; et al. JASPAR 2022: The 9th release of the open-access database of transcription factor binding profiles. Nucleic Acids Res. 2022, 50, D165–D173. [Google Scholar] [CrossRef] [PubMed]
- Kheradpour, P.; Ernst, J.; Melnikov, A.; Rogov, P.; Wang, L.; Zhang, X.; Alston, J.; Mikkelsen, T.S.; Kellis, M. Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel reporter assay. Genome Res. 2013, 23, 800–811. [Google Scholar] [CrossRef] [Green Version]
- Bergman, D.T.; Jones, T.R.; Liu, V.; Ray, J.; Jagoda, E.; Siraj, L.; Kang, H.Y.; Nasser, J.; Kane, M.; Rios, A.; et al. Compatibility rules of human enhancer and promoter sequences. Nature 2022, 607, 176–184. [Google Scholar] [CrossRef]
- Li, Y.; Chen, X.; Lu, C. The interplay between DNA and histone methylation: Molecular mechanisms and disease implications. EMBO Rep. 2021, 22, e51803. [Google Scholar] [CrossRef]
- Weinberg, D.N.; Rosenbaum, P.; Chen, X.; Barrows, D.; Horth, C.; Marunde, M.R.; Popova, I.K.; Gillespie, Z.B.; Keogh, M.C.; Lu, C.; et al. Two competing mechanisms of DNMT3A recruitment regulate the dynamics of de novo DNA methylation at PRC1-targeted CpG islands. Nat. Genet. 2021, 53, 794–800. [Google Scholar] [CrossRef]
- Fu, K.; Bonora, G.; Pellegrini, M. Interactions between core histone marks and DNA methyltransferases predict DNA methylation patterns observed in human cells and tissues. Epigenetics 2020, 15, 272–282. [Google Scholar] [CrossRef]
- Potthoff, M.J.; Arnold, M.A.; McAnally, J.; Richardson, J.A.; Bassel-Duby, R.; Olson, E.N. Regulation of skeletal muscle sarcomere integrity and postnatal muscle function by Mef2c. Mol. Cell. Biol. 2007, 27, 8143–8151. [Google Scholar] [CrossRef] [Green Version]
- Tierney, M.T.; Aydogdu, T.; Sala, D.; Malecova, B.; Gatto, S.; Puri, P.L.; Latella, L.; Sacco, A. STAT3 signaling controls satellite cell expansion and skeletal muscle repair. Nat. Med. 2014, 20, 1182–1186. [Google Scholar] [CrossRef] [Green Version]
- Ponnaluri, V.K.; Ehrlich, K.C.; Zhang, G.; Lacey, M.; Johnston, D.; Pradhan, S.; Ehrlich, M. Association of 5-hydroxymethylation and 5-methylation of DNA cytosine with tissue-specific gene expression. Epigenetics 2016, 12, 123–138. [Google Scholar] [CrossRef]
- Johansson, J.A.; Headon, D.J. Regionalisation of the skin. Semin. Cell Dev. Biol. 2014, 25–26, 3–10. [Google Scholar] [CrossRef] [PubMed]
- Ejarque, M.; Ceperuelo-Mallafré, V.; Serena, C.; Maymo-Masip, E.; Duran, X.; Díaz-Ramos, A.; Millan-Scheiding, M.; Núñez-Álvarez, Y.; Núñez-Roa, C.; Gama, P.; et al. Adipose tissue mitochondrial dysfunction in human obesity is linked to a specific DNA methylation signature in adipose-derived stem cells. Int. J. Obes. 2019, 43, 1256–1268. [Google Scholar] [CrossRef] [PubMed]
- Farin, H.F.; Bussen, M.; Schmidt, M.K.; Singh, M.K.; Schuster-Gossler, K.; Kispert, A. Transcriptional repression by the T-box proteins Tbx18 and Tbx15 depends on Groucho corepressors. J. Biol. Chem. 2007, 282, 25748–25759. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Y.; Li, J.; Ji, Y.; Cheng, Y.; Fu, X. Mutations in the TBX15-ADAMTS2 pathway associate with a novel soft palate dysplasia. Hum. Mutat. 2022. [Google Scholar] [CrossRef]
- Nagel, S.; Pommerenke, C.; Meyer, C.; MacLeod, R.A.F.; Drexler, H.G. Establishment of the TALE-code reveals aberrantly activated homeobox gene PBX1 in Hodgkin lymphoma. PLoS ONE 2021, 16, e0246603. [Google Scholar] [CrossRef]
- Tian, H.; He, Y.; Xue, Y.; Gao, Y.Q. Expression regulation of genes is linked to their CpG density distributions around transcription start sites. Life Sci. Alliance 2022, 5, e202101302. [Google Scholar] [CrossRef]
- De Micheli, A.J.; Spector, J.A.; Elemento, O.; Cosgrove, B.D. A reference single-cell transcriptomic atlas of human skeletal muscle tissue reveals bifurcated muscle stem cell populations. Skelet. Muscle 2020, 10, 19. [Google Scholar] [CrossRef]
- Ronaldson, S.M.; Stephenson, D.G.; Head, S.I. Calcium and strontium contractile activation properties of single skinned skeletal muscle fibres from elderly women 66-90 years of age. J. Muscle Res. Cell Motil. 2022, 43, 173–183. [Google Scholar] [CrossRef]
- Turner, D.C.; Seaborne, R.A.; Sharples, A.P. Comparative transcriptome and methylome analysis in human skeletal muscle anabolism, hypertrophy and epigenetic memory. Sci. Rep. 2019, 9, 4251. [Google Scholar] [CrossRef] [Green Version]
- Terry, E.E.; Zhang, X.; Hoffmann, C.; Hughes, L.D.; Lewis, S.A.; Li, J.; Wallace, M.J.; Riley, L.A.; Douglas, C.M.; Gutierrez-Monreal, M.A.; et al. Transcriptional profiling reveals extraordinary diversity among skeletal muscle tissues. Elife 2018, 7, e34613. [Google Scholar] [CrossRef]
- Voisin, S.; Jacques, M.; Landen, S.; Harvey, N.R.; Haupt, L.M.; Griffiths, L.R.; Gancheva, S.; Ouni, M.; Jähnert, M.; Ashton, K.J.; et al. Meta-analysis of genome-wide DNA methylation and integrative omics of age in human skeletal muscle. J. Cachexia Sarcopenia Muscle 2021, 12, 1064–1078. [Google Scholar] [CrossRef] [PubMed]
- Plotkin, D.L.; Roberts, M.D.; Haun, C.T.; Schoenfeld, B.J. Muscle Fiber Type Transitions with Exercise Training: Shifting Perspectives. Sports 2021, 9, 127. [Google Scholar] [CrossRef] [PubMed]
- Sarchielli, E.; Comeglio, P.; Filippi, S.; Cellai, I.; Guarnieri, G.; Guasti, D.; Rapizzi, E.; Rastrelli, G.; Bani, D.; Vannelli, G.; et al. Testosterone improves muscle fiber asset and exercise performance in a metabolic syndrome model. J. Endocrinol. 2020, 245, 259–279. [Google Scholar] [CrossRef] [PubMed]
- Dos Santos, M.; Backer, S.; Saintpierre, B.; Izac, B.; Andrieu, M.; Letourneur, F.; Relaix, F.; Sotiropoulos, A.; Maire, P. Single-nucleus RNA-seq and FISH identify coordinated transcriptional activity in mammalian myofibers. Nat. Commun. 2020, 11, 5102. [Google Scholar] [CrossRef] [PubMed]
- Delezie, J.; Weihrauch, M.; Maier, G.; Tejero, R.; Ham, D.J.; Gill, J.F.; Karrer-Cardel, B.; Rüegg, M.A.; Tabares, L.; Handschin, C. BDNF is a mediator of glycolytic fiber-type specification in mouse skeletal muscle. Proc. Natl. Acad. Sci. USA 2019, 116, 16111–16120. [Google Scholar] [CrossRef] [Green Version]
- Arbanas, J.; Klasan, G.S.; Nikolic, M.; Jerkovic, R.; Miljanovic, I.; Malnar, D. Fibre type composition of the human psoas major muscle with regard to the level of its origin. J. Anat. 2009, 215, 636–641. [Google Scholar] [CrossRef]
- Mendieta-Serrano, M.A.; Dhar, S.; Ng, B.H.; Narayanan, R.; Lee, J.J.Y.; Ong, H.T.; Toh, P.J.Y.; Röllin, A.; Roy, S.; Saunders, T.E. Slow muscles guide fast myocyte fusion to ensure robust myotome formation despite the high spatiotemporal stochasticity of fusion events. Dev. Cell 2022, 57, 2095–2110.e5. [Google Scholar] [CrossRef]
- Coletti, C.; Acosta, G.F.; Keslacy, S.; Coletti, D. Exercise-mediated reinnervation of skeletal muscle in elderly people: An update. Eur. J. Transl. Myol. 2022, 32, 10416. [Google Scholar] [CrossRef]
- Dikoglu, E.; Simsek-Kiper, P.O.; Utine, G.E.; Campos-Xavier, B.; Boduroglu, K.; Bonafe, L.; Superti-Furga, A.; Unger, S. Homozygosity for a novel truncating mutation confirms TBX15 deficiency as the cause of Cousin syndrome. Am. J. Med. Genet. A 2013, 161, 3161–3165. [Google Scholar] [CrossRef]
- Curry, G.A. Genetical and developmental studies on Droop-eared mice. Development 1959, 7, 39–65. [Google Scholar] [CrossRef]
- Yu, D.; Iwamura, Y.; Satou, Y.; Oda-Ishii, I. Tbx15/18/22 shares a binding site with Tbx6-r.b to maintain expression of a muscle structural gene in ascidian late embryos. Dev. Biol. 2021, 483, 1–12. [Google Scholar] [CrossRef] [PubMed]
- Qian, Y.; Xiong, Z.; Li, Y.; Kayser, M.; Liu, L.; Liu, F. The effects of Tbx15 and Pax1 on facial and other physical morphology in mice. FASEB Bioadv. 2021, 3, 1011–1019. [Google Scholar] [CrossRef] [PubMed]
- Tsumagari, K.; Chang, S.-C.; Lacey, M.; Baribault, C.; Chittur, S.V.; Sowden, J.; Tawil, R.; Crawford, G.E.; Ehrlich, M. Gene expression during normal and FSHD myogenesis. BMC Med. Genom. 2011, 4, 67. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, F.; Zhang, G.; Yu, L.; Feng, Y.; Li, X.; Zhang, Z.; Wang, Y.; Sun, D.; Pradhan, S. High-efficiency generation of induced pluripotent mesenchymal stem cells from human dermal fibroblasts using recombinant proteins. Stem Cell Res. Ther. 2016, 7, 99. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, Z.; Vaisvila, R.; Hussong, L.M.; Yan, B.; Baum, C.; Saleh, L.; Samaranayake, M.; Guan, S.; Dai, N.; Corrêa, I.R., Jr.; et al. Nondestructive enzymatic deamination enables single-molecule long-read amplicon sequencing for the determination of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution. Genome Res. 2021, 31, 291–300. [Google Scholar] [CrossRef] [PubMed]
- Laurent, L.; Wong, E.; Li, G.; Huynh, T.; Tsirigos, A.; Ong, C.T.; Low, H.M.; Kin Sung, K.W.; Rigoutsos, I.; Loring, J.; et al. Dynamic changes in the human methylome during differentiation. Genome Res. 2010, 20, 320–331. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pidsley, R.; Zotenko, E.; Peters, T.J.; Lawrence, M.G.; Risbridger, G.P.; Molloy, P.; Van Djik, S.; Muhlhausler, B.; Stirzaker, C.; Clark, S.J. Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling. Genome Biol. 2016, 17, 208. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hon, G.C.; Hawkins, R.D.; Caballero, O.L.; Lo, C.; Lister, R.; Pelizzola, M.; Valsesia, A.; Ye, Z.; Kuan, S.; Edsall, L.E.; et al. Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer. Genome Res. 2012, 22, 246–258. [Google Scholar] [CrossRef] [Green Version]
- Lister, R.; Pelizzola, M.; Dowen, R.H.; Hawkins, R.D.; Hon, G.; Tonti-Filippini, J.; Nery, J.R.; Lee, L.; Ye, Z.; Ngo, Q.M.; et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 2009, 462, 315–322. [Google Scholar] [CrossRef] [Green Version]
- Lacey, M.; Baribault, C.; Ehrlich, K.C.; Ehrlich, M. Data showing atherosclerosis-associated differentially methylated regions are often at enhancers. Data Brief 2019, 23, 103812. [Google Scholar] [CrossRef]
- Lacey, M.R.; Baribault, C.; Ehrlich, M. Modeling, simulation and analysis of methylation profiles from reduced representation bisulfite sequencing experiments. Stat. Appl. Genet. Mol. Biol. 2013, 12, 723–742. [Google Scholar] [CrossRef] [PubMed]
- Wang, E.T.; Sandberg, R.; Luo, S.; Khrebtukova, I.; Zhang, L.; Mayr, C.; Kingsmore, S.F.; Schroth, G.P.; Burge, C.B. Alternative isoform regulation in human tissue transcriptomes. Nature 2008, 456, 470–476. [Google Scholar] [CrossRef] [PubMed]
- Cao, J.; O’Day, D.R.; Pliner, H.A.; Kingsley, P.D.; Deng, M.; Daza, R.M.; Zager, M.A.; Aldinger, K.A.; Blecher-Gonen, R.; Zhang, F.; et al. A human cell atlas of fetal gene expression. Science 2020, 370, eaba7721. [Google Scholar] [CrossRef]
- Kodzius, R.; Kojima, M.; Nishiyori, H.; Nakamura, M.; Fukuda, S.; Tagami, M.; Sasaki, D.; Imamura, K.; Kai, C.; Harbers, M.; et al. CAGE: Cap analysis of gene expression. Nat. Methods 2006, 3, 211–222. [Google Scholar] [CrossRef] [PubMed]
- Terragni, J.; Zhang, G.; Sun, Z.; Pradhan, S.; Song, L.; Crawford, G.E.; Lacey, M.; Ehrlich, M. Notch signaling genes: Myogenic DNA hypomethylation and 5-hydroxymethylcytosine. Epigenetics 2014, 9, 842–850. [Google Scholar] [CrossRef] [PubMed]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ehrlich, K.C.; Lacey, M.; Baribault, C.; Sen, S.; Esteve, P.O.; Pradhan, S.; Ehrlich, M. Promoter-Adjacent DNA Hypermethylation Can Downmodulate Gene Expression: TBX15 in the Muscle Lineage. Epigenomes 2022, 6, 43. https://doi.org/10.3390/epigenomes6040043
Ehrlich KC, Lacey M, Baribault C, Sen S, Esteve PO, Pradhan S, Ehrlich M. Promoter-Adjacent DNA Hypermethylation Can Downmodulate Gene Expression: TBX15 in the Muscle Lineage. Epigenomes. 2022; 6(4):43. https://doi.org/10.3390/epigenomes6040043
Chicago/Turabian StyleEhrlich, Kenneth C., Michelle Lacey, Carl Baribault, Sagnik Sen, Pierre Olivier Esteve, Sriharsa Pradhan, and Melanie Ehrlich. 2022. "Promoter-Adjacent DNA Hypermethylation Can Downmodulate Gene Expression: TBX15 in the Muscle Lineage" Epigenomes 6, no. 4: 43. https://doi.org/10.3390/epigenomes6040043
APA StyleEhrlich, K. C., Lacey, M., Baribault, C., Sen, S., Esteve, P. O., Pradhan, S., & Ehrlich, M. (2022). Promoter-Adjacent DNA Hypermethylation Can Downmodulate Gene Expression: TBX15 in the Muscle Lineage. Epigenomes, 6(4), 43. https://doi.org/10.3390/epigenomes6040043