Sự điều chỉnh sai lệch biểu sinh của các miền liên kết màng trong hội chứng progeria Hutchinson-Gilford

Florian Köhler1, Felix Bormann1, Günter Raddatz1, Julian Gutekunst1, Nick Gilbert2, Tanja Musch1, Anke S. Lonsdorf3, Sylvia Erhardt2, Frank Lyko1, Manuel Rodríguez-Paredes1
1Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany
2Center for Molecular Biology of Heidelberg University (ZMBH), Im Neuenheimer Feld 282, 69120 Heidelberg, Germany
3Department of Dermatology, University Hospital, Ruprecht-Karls University of Heidelberg, Heidelberg, Germany

Tóm tắt

Tóm tắt Giới thiệu Hội chứng progeria Hutchinson-Gilford (HGPS) là một bệnh progeroid đặc trưng bởi sự khởi phát sớm của các kiểu hình liên quan đến tuổi tác, bao gồm viêm khớp, mất mỡ cơ thể và tóc, cùng với xơ vữa động mạch. Các tế bào từ những người bị ảnh hưởng thể hiện một phiên bản đột biến của protein màng nhân lamin A (được gọi là progerin) và trước đây đã được chứng minh là có sự thay đổi rõ rệt trong các biến đổi histone. Phương pháp Tại đây, chúng tôi phân tích khả năng rằng sự điều chỉnh sai lệch biểu sinh của các miền liên kết màng (LADs) có liên quan đến bệnh lý phân tử của HGPS. Để thực hiện điều này, chúng tôi đã nghiên cứu khả năng tiếp cận chromatin (Assay for Transposase-accessible Chromatin (ATAC)-see/-seq), hồ sơ metyl hóa DNA (Infinium MethylationEPIC BeadChips) và gen transcriptomes (RNA-seq) của chín dòng tế bào nguyên thủy HGPS và sáu đối chứng bổ sung, hai dòng tế bào fibroblast mẹ và bốn dòng tế bào fibroblast khỏe mạnh cùng độ tuổi.

Từ khóa

#Hội chứng progeria Hutchinson-Gilford #sự điều chỉnh sai lệch biểu sinh #các miền liên kết màng #biến đổi histone #metyl hóa DNA

Tài liệu tham khảo

Gerace L, Blobel G. The nuclear envelope lamina is reversibly depolymerized during mitosis. Cell. 1980;19:277–87.

Höger TH, Zatloukal K, Waizenegger I, Krohne G. Characterization of a second highly conserved B-type lamin present in cells previously thought to contain only a single B-type lamin. Chromosoma. 1990;99:379–90.

Capell BC, Collins FS. Human laminopathies: nuclei gone genetically awry. Nat Rev Genet. 2006;7:940–52.

Hennekam RC. Hutchinson-Gilford progeria syndrome: review of the phenotype. Am J Med Genet. 2006;140:2603–24.

Merideth MA, Gordon LB, Clauss S, Sachdev V, Smith ACM, Perry MB, et al. Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med. 2008;358:592–604.

Goldman RD, Shumaker DK, Erdos MR, Eriksson M, Goldman AE, Gordon LB, et al. Accumulation of mutant lamin A progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci U S A. 2004;101:8963–8.

Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, et al. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature. 2003;423:293–8.

De Sandre-Giovannoli A, Bernard R, Cau P, Navarro C, Amiel J, Boccaccio I, et al. Lamin A truncation in Hutchinson-Gilford progeria. Science. 2003;300:2055.

Baker PB, Baba N, Boesel CP. Cardiovascular abnormalities in progeria. Case report and review of the literature. Arch Pathol Lab Med. 1981;105:384–6.

Viteri G, Chung YW, Stadtman ER. Effect of progerin on the accumulation of oxidized proteins in fibroblasts from Hutchinson Gilford progeria patients. Mech Ageing Dev. 2010;131:2–8.

Kubben N, Zhang W, Wang L, Voss TC, Yang J, Qu J, et al. Repression of the antioxidant NRF2 pathway in premature aging. Cell. 2016;165:1361–74.

Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X, et al. Genomic instability in laminopathy-based premature aging. Nat Med. 2005;11:780–5.

Liu Y, Rusinol A, Sinensky M, Wang Y, Zou Y. DNA damage responses in progeroid syndromes arise from defective maturation of prelamin A. J Cell Sci. 2006;119:4644–9.

Decker ML, Chavez E, Vulto I, Lansdorp PM. Telomere length in Hutchinson-Gilford Progeria syndrome. Mech Ageing Dev. 2009;130:377–83.

Scaffidi P, Misteli T. Lamin A-dependent nuclear defects in human aging. Science. 2006;312:1059–63.

Cao K, Capell BC, Erdos MR, Djabali K, Collins FS. A lamin A protein isoform overexpressed in Hutchinson-Gilford progeria syndrome interferes with mitosis in progeria and normal cells. Proc Natl Acad Sci U S A. 2007;104:4949–54.

McClintock D, Ratner D, Lokuge M, Owens DM, Gordon LB, Collins FS, et al. The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin. PLoS One. 2007;2:e1269.

Shumaker DK, Dechat T, Kohlmaier A, Adam SA, Bozovsky MR, Erdos MR, et al. Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci U S A. 2006;103:8703–8.

McCord RP, Nazario-Toole A, Zhang H, Chines PS, Zhan Y, Erdos MR, et al. Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson-Gilford progeria syndrome. Genome Res. 2013;23:260–9.

Liu B, Wang Z, Zhang L, Ghosh S, Zheng H, Zhou Z. Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model. Nat Commun. 2013;4:1868.

Chandra T, Ewels PA, Schoenfelder S, Furlan-Magaril M, Wingett SW, Kirschner K, et al. Global reorganization of the nuclear landscape in senescent cells. Cell Rep. 2015;10:471–83.

Deng J, Shoemaker R, Xie B, Gore A, Leproust EM, Antosiewicz-Bourget J, et al. Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming. Nat Biotechnol. 2009;27:353–60.

Liu GH, Barkho BZ, Ruiz S, Diep D, Qu J, Yang SL, et al. Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature. 2011;472:221–7.

Heyn H, Moran S, Esteller M. Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford progeria and Werner syndrome. Epigenetics. 2013;8:28–33.

Horvath S, Oshima J, Martin GM, Lu AT, Quach A, Cohen H, et al. Epigenetic clock for skin and blood cells applied to Hutchinson Gilford progeria syndrome and ex vivo studies. Aging (Albany NY). 2018;10:1758–75.

Guelen L, Pagie L, Brasset E, Meuleman W, Faza MB, Talhout W, et al. Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature. 2008;453:948–51.

Peric-Hupkes D, Meuleman W, Pagie L, Bruggeman SWM, Solovei I, Brugman W, et al. Molecular maps of the reorganization of genome-nuclear lamina interactions during differentiation. Mol Cell. 2010;38:603–13.

van Steensel B, Belmont AS. Lamina-associated domains: links with chromosome architecture, heterochromatin, and gene repression. Cell. 2017;169:780–91.

Wen B, Wu H, Shinkai Y, Irizarry RA, Feinberg AP. Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells. Nat Genet. 2009;41:246–50.

Berman BP, Weisenberger DJ, Aman JF, Hinoue T, Ramjan Z, Liu Y, et al. Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains. Nat Genet. 2011;44:40–6.

Xie WJ, Meng L, Liu S, Zhang L, Cai X, Gao YQ. Structural modeling of chromatin integrates genome features and reveals chromosome folding principle. Sci Rep. 2017;7:2818.

Zhou W, Dinh HQ, Ramjan Z, Weisenberger DJ, Nicolet CM, Shen H, et al. DNA methylation loss in late-replicating domains is linked to mitotic cell division. Nat Genet. 2018;50:591–602.

Chen X, Shen Y, Draper W, Buenrostro JD, Litzenburger U, Cho SW, et al. ATAC-see reveals the accessible genome by transposase-mediated imaging and sequencing. Nat Methods. 2016;13:1013–20.

Buenrostro JD, Wu B, Chang HY, Greenleaf WJ. ATAC-seq: a method for assaying chromatin accessibility genome-wide. Curr Protoc Mol Biol. 2015;109:21.29.1–9.

Köhler F, Bormann F, Raddatz G, Gutekunst J, Corless S, Musch T, et al. Epigenetic deregulation of lamina-associated domains in Hutchinson-Gilford progeria syndrome. ATAC-seq and RNA-seq datasets. Gene Expression Omnibus (GEO). (2020). https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE150138. Accessed 8 May 2020.

Langmead B, Salzberg SL. Fast gapped-read alignment with bowtie 2. Nat Methods. 2012;9:357–9.

Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 2008;9:R137.

Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.

ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57–74.

Davis CA, Hitz BC, Sloan CA, Chan ET, Davidson JM, Gabdank I, et al. The encyclopedia of DNA elements (ENCODE): data portal update. Nucleic Acids Res. 2018;46:D794–801.

Lund EG, Duband-Goulet I, Oldenburg A, Buendia B, Collas P. Distinct features of lamin A-interacting chromatin domains mapped by ChIP-sequencing from sonicated or micrococcal nuclease-digested chromatin. Nucleus. 2015;6:30–9.

Vadrot N, Duband-Goulet I, Cabet E, Attanda W, Barateau A, Vicart P, et al. The p.R482W substitution in a-type lamins deregulates SREBP1 activity in Dunnigan-type familial partial lipodystrophy. Hum Mol Genet. 2015;24:2096–109.

Lund E, Oldenburg AR, Collas P. Enriched domain detector: a program for detection of wide genomic enrichment domains robust against local variations. Nucleic Acids Res. 2014;42:e92.

Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38:576–89.

Köhler F, Bormann F, Raddatz G, Gutekunst J, Corless S, Musch T, et al. Epigenetic deregulation of lamina-associated domains in Hutchinson-Gilford Progeria Syndrome. Infinium MethylationEPIC Beadchip datasets. Gene Expression Omnibus (GEO). (2020). https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE149960. Accessed 7 May 2020.

Aryee MJ, Jaffe AE, Corrada-Bravo H, Ladd-Acosta C, Feinberg AP, Hansen KD, et al. Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics. 2014;30:1363–9.

Wilkerson MD, Hayes DN. ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics. 2010;26:1572–3.

Lê S, Josse J, Husson F. FactoMineR: an R package for multivariate analysis. J Stat Softw. 2008;25:1–18.

Yao L, Shen H, Laird PW, Farnham PJ, Berman BP. Inferring regulatory element landscapes and transcription factor networks from cancer methylomes. Genome Biol. 2015;16:105.

Silva TC, Coetzee SG, Gull N, Yao L, Hazelett DJ, Noushmehr H, et al. ELmer v.2: an r/bioconductor package to reconstruct gene regulatory networks from DNA methylation and transcriptome profiles. Bioinformatics. 2019;35:1974–7.

Rinaldi L, Datta D, Serrat J, Morey L, Solanas G, Avgustinova A, et al. Dnmt3a and Dnmt3b associate with enhancers to regulate human epidermal stem cell homeostasis. Cell Stem Cell. 2016;19:491–501.

Wagner JR, Busche S, Ge B, Kwan T, Pastinen T, Blanchette M. The relationship between DNA methylation, genetic and expression inter-individual variation in untransformed human fibroblasts. Genome Biol. 2014;15:R37.

Maierhofer A, Flunkert J, Oshima J, Martin GM, Poot M, Nanda I, et al. Epigenetic signatures of Werner syndrome occur early in life and are distinct from normal epigenetic aging processes. Aging Cell. 2019;18:e12995.

Schlegelberger B, Metzke S, Harder S, Zühlke-Jenisch R, Zhang Y, Siebert R. Classical and molecular cytogenetics of tumor cells. In: Wegner RD, editor. Diagnostic Cytogenetics. Heidelberg: Springer; 1999. p. 151–85.

Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9:676–82.

Rueden CT, Schindelin J, Hiner MC, DeZonia BE, Walter AE, Arena ET, et al. ImageJ2: ImageJ for the next generation of scientific image data. BMC Bioinformatics. 2017;18:529.

Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 2013;14:R36.

Trapnell C, Hendrickson DG, Sauvageau M, Goff L, Rinn JL, Pachter L. Differential analysis of gene regulation at transcript resolution with RNA-seq. Nat Biotechnol. 2013;31:46–53.

Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene Ontology: tool for the unification of biology. Nat Genet. 2000;25:25–9.

Carbon S, Dietze H, Lewis SE, Mungall CJ, Munoz-Torres MC, Basu S, et al. Expansion of the gene ontology knowledgebase and resources: the gene ontology consortium. Nucleic Acids Res. 2017;45:D331–8.

Carbon S, Ireland A, Mungall CJ, Shu S, Marshall B, Lewis S, et al. AmiGO: online access to ontology and annotation data. Bioinformatics. 2009;25:288–9.

Matys V. TRANSFAC(R) and its module TRANSCompel(R): transcriptional gene regulation in eukaryotes. Nucleic Acids Res. 2006;34:D108–10.

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert B, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102:15545–50.

Liberzon A, Birger C, Thorvaldsdóttir H, Ghandi M, Mesirov JP, Tamayo P. The molecular signatures database Hallmark gene set collection. Cell Syst. 2015;1:417–25.

Fleischer JG, Schulte R, Tsai HH, Tyagi S, Ibarra A, Shokhirev MN, et al. Predicting age from the transcriptome of human dermal fibroblasts. Genome Biol. 2018;19:221.

Mehta IS, Eskiw CH, Arican HD, Kill IR, Bridger JM. Farnesyltransferase inhibitor treatment restores chromosome territory positions and active chromosome dynamics in Hutchinson-Gilford progeria syndrome cells. Genome Biol. 2011;12:R74.

Kind J, Pagie L, De Vries SS, Dekker J, Van Oudenaarden A, Kind J, et al. Genome-wide maps of nuclear lamina interactions in single human cells article genome-wide maps of nuclear lamina interactions in single human cells. Cell. 2015;163:134–47.

Ivorra C, Kubicek M, González JM, Sanz-González SM, Álvarez-Barrientos A, O’Connor JE, et al. A mechanism of AP-1 suppression through interaction of c-Fos with lamin A/C. Genes Dev. 2006;20:307–20.

Chinenov Y, Kerppola TK. Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity. Oncogene. 2001;20:2438–52.

Hess J, Angel P, Schorpp-Kistner M. AP-1 subunits: quarrel and harmony among siblings. J Cell Sci. 2004;117:5965–73.

Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, Gomez A, et al. Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci U S A. 2012;109:10522–7.

Zampieri M, Ciccarone F, Calabrese R, Franceschi C, Bürkle A, Caiafa P. Reconfiguration of DNA methylation in aging. Mech Ageing Dev. 2015;151:60–70.

Maierhofer A, Flunkert J, Oshima J, Martin GM, Haaf T, Horvath S. Accelerated epigenetic aging in Werner syndrome. Aging (Albany NY). 2017;9:1143–52.

Csoka AB, English SB, Simkevich CP, Ginzinger DG, Butte AJ, Schatten GP, et al. Genome-scale expression profiling of Hutchinson-Gilford progeria syndrome reveals widespread transcriptional misregulation leading to mesodermal/mesenchymal defects and accelarated atherosclerosis. Aging Cell. 2004;3:235–43.

Aoka Y, Johnson FL, Penta K, Hirata KI, Hidai C, Schatzman R, et al. The embryonic angiogenic factor Del1 accelerates tumor growth by enhancing vascular formation. Microvasc Res. 2002;64:148–61.

Hidai C, Zupancic T, Penta K, Mikhail A, Kawana M, Quertermous EE, et al. Cloning and characterization of developmental endothelial locus-1: an embryonic endothelial cell protein that binds the αvβ3 integrin receptor. Genes Dev. 1998;12:21–33.

Wilson HMP, Birnbaum RS, Poot M, Quinn LBS, Swisshelm K. Insulin-like growth factor binding protein-related protein 1 inhibits proliferation of MCF-7 breast cancer cells via a senescence-like mechanism. Cell Growth Differ. 2002;13:205–13.

Wajapeyee N, Serra RW, Zhu X, Mahalingam M, Green MR. Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell. 2008;132:363–74.

Pen A, Moreno MJ, Durocher Y, Deb-Rinker P, Stanimirovic DB. Glioblastoma-secreted factors induce IGFBP7 and angiogenesis by modulating Smad-2-dependent TGF-β signaling. Oncogene. 2008;27:6834–44.

Baubec T, Colombo DF, Wirbelauer C, Schmidt J, Burger L, Krebs AR, et al. Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation. Nature. 2015;520:243–7.

McEwen LM, Jones MJ, Lin DTS, Edgar RD, Husquin LT, MacIsaac JL, et al. Systematic evaluation of DNA methylation age estimation with common preprocessing methods and the Infinium MethylationEPIC BeadChip array. Clin Epigenetics. 2018;10:123.

Zheng X, Hu J, Yue S, Kristiani L, Kim M, Sauria M, et al. Lamins organize the global three-dimensional genome from the nuclear periphery. Mol Cell. 2018;71:802–15.e7.

Heessen S, Fornerod M. The inner nuclear envelope as a transcription factor resting place. EMBO Rep. 2007;8:914–9.

Fishilevich S, Nudel R, Rappaport N, Hadar R, Plaschkes I, Iny Stein T, et al. GeneHancer: genome-wide integration of enhancers and target genes in GeneCards. Database (Oxford). 2017;2017:bax028.