title: PML bodies provide an important platform for the maintenance of telomeric chromatin integrity in embryonic stem cells.
abstract: We have previously shown that α-thalassemia mental retardation X-linked (ATRX) and histone H3.3 are key regulators of telomeric chromatin in mouse embryonic stem cells. The function of ATRX and H3.3 in the maintenance of telomere chromatin integrity is further demonstrated by recent studies that show the strong association of ATRX/H3.3 mutations with alternative lengthening of telomeres in telomerase-negative human cancer cells. Here, we demonstrate that ATRX and H3.3 co-localize with the telomeric DNA and associated proteins within the promyelocytic leukemia (PML) bodies in mouse ES cells. The assembly of these telomere-associated PML bodies is most prominent at S phase. RNA interference (RNAi)-mediated knockdown of PML expression induces the disassembly of these nuclear bodies and a telomere dysfunction phenotype in mouse ES cells. Loss of function of PML bodies in mouse ES cells also disrupts binding of ATRX/H3.3 and proper establishment of histone methylation pattern at the telomere. Our study demonstrates that PML bodies act as epigenetic regulators by serving as platforms for the assembly of the telomeric chromatin to ensure a faithful inheritance of epigenetic information at the telomere.
authors: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors: Fiona T M
authors: FT
authors: Chang
authors: James D
authors: JD
authors: McGhie
authors: F Lyn
authors: FL
authors: Chan
authors: Michelle C
authors: MC
authors: Tang
authors: Melissa A
authors: MA
authors: Anderson
authors: Jeffrey R
authors: JR
authors: Mann
authors: K H
authors: KH
authors: Andy Choo
authors: Lee H
authors: LH
authors: Wong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D022003:Cell Nucleus Structures / Q000737:chemistry / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D004265:DNA Helicases / Q000032:analysis; D004260:DNA Repair; D053595:Embryonic Stem Cells / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006657:Histones / Q000032:analysis; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000032:analysis / Q000502:physiology; D010641:Phenotype; D016196:S Phase; D016615:Telomere / Q000378:metabolism*; D000075924:X-linked Nuclear Protein
chemical_list: D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D004265:DNA Helicases; C490462:Atrx protein, mouse; D000075924:X-linked Nuclear Protein