8c866f34d391484a59df5176a3f005ce 270586.pdf df8b2a6846f3ff8fa906a312049ac15f7065f37c 270586.pdf a7167480390dff2df75b06f2af1eab42e5e2a5f6fca78fb16a01196dc2237844 270586.pdf Title: The Role of MacroH2A Histone Variants in Cancer Subject: The epigenome regulates gene expression and provides a molecular memory of cellular events. A growing body of evidence has highlighted the importance of epigenetic regulation in physiological tissue homeostasis and malignant transformation. Among epigenetic mechanisms, the replacement of replication-coupled histones with histone variants is the least understood. Due to differences in protein sequence and genomic distribution, histone variants contribute to the plasticity of the epigenome. Here, we focus on the family of macroH2A histone variants that are particular in having a tripartite structure consisting of a histone fold, an intrinsically disordered linker and a globular macrodomain. We discuss how these domains mediate different molecular functions related to chromatin architecture, transcription and DNA repair. Dysregulated expression of macroH2A histone variants has been observed in different subtypes of cancer and has variable prognostic impact, depending on cellular context and molecular background. We aim to provide a concise review regarding the context- and isoform-dependent contributions of macroH2A histone variants to cancer development and progression. Keywords: macroH2A; histone variants; epigenetics; chromatin; cancer; macrodomain; tumor suppressor; oncohistone; malignant transformation Author: Chen-Jen Hsu, Oliver Meers, Marcus Buschbeck and Florian H. Heidel Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Jun 16 08:16:18 2021 CEST ModDate: Wed Jun 16 08:18:20 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1053208 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- EUNPSG+URWPalladioL-Ital Type 1 Custom yes yes no 10 0 FEOLFE+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 UWVNWF+URWPalladioL-Roma Type 1 Custom yes yes no 19 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 28 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 50 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 54 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 58 0 DFDOEP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 73 0 DFDOFB+PalatinoLinotype TrueType WinAnsi yes yes no 76 0 DFDOFD+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 79 0 GOCQIR+EURM10 Type 1 Builtin yes yes no 86 0 DFDOEP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 99 0 DFDOFB+PalatinoLinotype TrueType WinAnsi yes yes no 102 0 DFDOFD+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 105 0 HHFREY+EURM7 Type 1 Builtin yes yes no 124 0 NQHFUT+VnURWPalladioL Type 1 Custom yes yes no 131 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 03:08:26 CEST RepresentationInformation: 270586.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 12:05:02 CEST Size: 1053208 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 602 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Alteration of H2A Variants in Cancer Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: MacroH2A Variants: The Three Functional Domains Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: The Ambiguous Role of MacroH2A in Transcriptional Regulation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: MacroH2A as a Tumor Suppressor Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: MacroH2A as an Oncohistone Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Info: Title: The Role of MacroH2A Histone Variants in Cancer Author: Chen-Jen Hsu, Oliver Meers, Marcus Buschbeck and Florian H. Heidel Subject: The epigenome regulates gene expression and provides a molecular memory of cellular events. A growing body of evidence has highlighted the importance of epigenetic regulation in physiological tissue homeostasis and malignant transformation. Among epigenetic mechanisms, the replacement of replication-coupled histones with histone variants is the least understood. Due to differences in protein sequence and genomic distribution, histone variants contribute to the plasticity of the epigenome. Here, we focus on the family of macroH2A histone variants that are particular in having a tripartite structure consisting of a histone fold, an intrinsically disordered linker and a globular macrodomain. We discuss how these domains mediate different molecular functions related to chromatin architecture, transcription and DNA repair. Dysregulated expression of macroH2A histone variants has been observed in different subtypes of cancer and has variable prognostic impact, depending on cellular context and molecular background. We aim to provide a concise review regarding the context- and isoform-dependent contributions of macroH2A histone variants to cancer development and progression. 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Annotation: Subtype: Link Rect: 211, 618, 249, 628 Annotation: Subtype: Link Rect: 255, 618, 291, 628 Annotation: Subtype: Link Rect: 289, 594, 326, 605 Annotation: Subtype: Link Rect: 333, 594, 369, 605 Annotation: Subtype: Link Rect: 73, 572, 110, 582 Annotation: Subtype: Link Rect: 117, 572, 153, 582 Annotation: Subtype: Link Rect: 365, 537, 403, 548 Annotation: Subtype: Link Rect: 409, 537, 445, 548 Annotation: Subtype: Link Rect: 122, 503, 159, 513 Annotation: Subtype: Link Rect: 166, 503, 202, 513 Annotation: Subtype: Link Rect: 104, 469, 141, 479 Annotation: Subtype: Link Rect: 59, 434, 97, 444 Annotation: Subtype: Link Rect: 294, 410, 331, 421 Annotation: Subtype: Link Rect: 337, 410, 373, 421 Annotation: Subtype: Link Rect: 447, 387, 484, 398 Annotation: Subtype: Link Rect: 109, 365, 146, 375 Annotation: Subtype: Link Rect: 153, 365, 189, 375 Annotation: Subtype: Link Rect: 108, 331, 146, 341 Annotation: Subtype: Link Rect: 152, 331, 188, 341 Annotation: Subtype: Link Rect: 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Rect: 148, 250, 184, 260 Annotation: Subtype: Link Rect: 429, 226, 467, 237 Annotation: Subtype: Link Rect: 196, 192, 234, 203 Annotation: Subtype: Link Rect: 240, 192, 276, 203 Annotation: Subtype: Link Rect: 196, 169, 234, 180 Annotation: Subtype: Link Rect: 237, 134, 275, 145 Annotation: Subtype: Link Rect: 59, 112, 97, 122 Annotation: Subtype: Link Rect: 376, 88, 414, 99 Annotation: Subtype: Link Rect: 385, 65, 423, 76 Page: Sequence: 16 Annotations: Annotation: Subtype: Link Rect: 291, 721, 328, 732 Annotation: Subtype: Link Rect: 104, 687, 141, 697 Annotation: Subtype: Link Rect: 519, 663, 557, 674 Annotation: Subtype: Link Rect: 59, 653, 95, 663 Annotation: Subtype: Link Rect: 434, 629, 472, 640 Annotation: Subtype: Link Rect: 478, 629, 514, 640 Annotation: Subtype: Link Rect: 346, 594, 383, 605 Annotation: Subtype: Link Rect: 389, 594, 425, 605 Annotation: Subtype: Link Rect: 479, 571, 516, 582 Annotation: Subtype: Link Rect: 521, 571, 557, 582 Annotation: Subtype: Link Rect: 159, 538, 196, 548 Annotation: Subtype: Link Rect: 95, 503, 133, 513 Annotation: Subtype: Link Rect: 200, 480, 238, 490 Annotation: Subtype: Link Rect: 244, 480, 280, 490 Annotation: Subtype: Link Rect: 260, 456, 298, 467 Annotation: Subtype: Link Rect: 476, 445, 514, 456 Annotation: Subtype: Link Rect: 433, 422, 470, 433 Annotation: Subtype: Link Rect: 382, 399, 420, 410 Annotation: Subtype: Link Rect: 59, 365, 97, 375 Annotation: Subtype: Link Rect: 103, 365, 139, 375 Annotation: Subtype: Link Rect: 59, 331, 97, 341 Annotation: Subtype: Link Rect: 103, 331, 139, 341 Annotation: Subtype: Link Rect: 188, 295, 225, 306 Annotation: Subtype: Link Rect: 231, 295, 267, 306 Annotation: Subtype: Link Rect: 429, 272, 466, 283 Annotation: Subtype: Link Rect: 59, 238, 97, 249 Annotation: Subtype: Link Rect: 104, 204, 141, 214 Annotation: Subtype: Link Rect: 440, 180, 477, 191 Annotation: Subtype: Link Rect: 519, 157, 557, 168 Annotation: Subtype: Link Rect: 59, 146, 95, 157 Checksum: cfc86732 Type: CRC32 Checksum: 8c866f34d391484a59df5176a3f005ce Type: MD5 Checksum: df8b2a6846f3ff8fa906a312049ac15f7065f37c Type: SHA-1