title: Directed targeting of chromatin to the nuclear lamina is mediated by chromatin state and A-type lamins.
abstract: Nuclear organization has been implicated in regulating gene activity. Recently, large developmentally regulated regions of the genome dynamically associated with the nuclear lamina have been identified. However, little is known about how these lamina-associated domains (LADs) are directed to the nuclear lamina. We use our tagged chromosomal insertion site system to identify small sequences from borders of fibroblast-specific variable LADs that are sufficient to target these ectopic sites to the nuclear periphery. We identify YY1 (Ying-Yang1) binding sites as enriched in relocating sequences. Knockdown of YY1 or lamin A/C, but not lamin A, led to a loss of lamina association. In addition, targeted recruitment of YY1 proteins facilitated ectopic LAD formation dependent on histone H3 lysine 27 trimethylation and histone H3 lysine di- and trimethylation. Our results also reveal that endogenous loci appear to be dependent on lamin A/C, YY1, H3K27me3, and H3K9me2/3 for maintenance of lamina-proximal positioning.
authors.affiliation: Department of Biological Chemistry, Center for Epigenetics, and Department of Oncology Biostatistics and Bioinformatics, Johns Hopkins University, Baltimore, MD 21205 Department of Biological Chemistry, Center for Epigenetics, and Department of Oncology Biostatistics and Bioinformatics, Johns Hopkins University, Baltimore, MD 21205.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Harr
authors.affiliation: Department of Biological Chemistry, Center for Epigenetics, and Department of Oncology Biostatistics and Bioinformatics, Johns Hopkins University, Baltimore, MD 21205 Department of Biological Chemistry, Center for Epigenetics, and Department of Oncology Biostatistics and Bioinformatics, Johns Hopkins University, Baltimore, MD 21205.
authors.forename: Teresa Romeo
authors.initials: TR
authors.lastname: Luperchio
authors.affiliation: Department of Biological Chemistry, Center for Epigenetics, and Department of Oncology Biostatistics and Bioinformatics, Johns Hopkins University, Baltimore, MD 21205 Department of Biological Chemistry, Center for Epigenetics, and Department of Oncology Biostatistics and Bioinformatics, Johns Hopkins University, Baltimore, MD 21205.
authors.forename: Xianrong
authors.initials: X
authors.lastname: Wong
authors.affiliation: Department of Biological Chemistry, Center for Epigenetics, and Department of Oncology Biostatistics and Bioinformatics, Johns Hopkins University, Baltimore, MD 21205 Department of Biological Chemistry, Center for Epigenetics, and Department of Oncology Biostatistics and Bioinformatics, Johns Hopkins University, Baltimore, MD 21205.
authors.forename: Erez
authors.initials: E
authors.lastname: Cohen
authors.affiliation: Department of Biological Chemistry, Center for Epigenetics, and Department of Oncology Biostatistics and Bioinformatics, Johns Hopkins University, Baltimore, MD 21205.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Wheelan
authors.affiliation: Department of Biological Chemistry, Center for Epigenetics, and Department of Oncology Biostatistics and Bioinformatics, Johns Hopkins University, Baltimore, MD 21205 Department of Biological Chemistry, Center for Epigenetics, and Department of Oncology Biostatistics and Bioinformatics, Johns Hopkins University, Baltimore, MD 21205 kreddy4@jhmi.edu.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Reddy
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D001665:Binding Sites; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D008239:Lysine; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D034881:Nuclear Lamina / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D050986:YY1 Transcription Factor / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D034904:Lamin Type A; C576142:Lmna protein, mouse; C499308:Rag2 protein, mouse; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse; D008239:Lysine