title: Tissue homogeneity requires inhibition of unequal gene silencing during development.
abstract: Multicellular organisms can generate and maintain homogenous populations of cells that make up individual tissues. However, cellular processes that can disrupt homogeneity and how organisms overcome such disruption are unknown. We found that ∼100-fold differences in expression from a repetitive DNA transgene can occur between intestinal cells in Caenorhabditis elegans These differences are caused by gene silencing in some cells and are actively suppressed by parental and zygotic factors such as the conserved exonuclease ERI-1. If unsuppressed, silencing can spread between some cells in embryos but can be repeat specific and independent of other homologous loci within each cell. Silencing can persist through DNA replication and nuclear divisions, disrupting uniform gene expression in developed animals. Analysis at single-cell resolution suggests that differences between cells arise during early cell divisions upon unequal segregation of an initiator of silencing. Our results suggest that organisms with high repetitive DNA content, which include humans, could use similar developmental mechanisms to achieve and maintain tissue homogeneity.
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742.
authors.forename: Hai H
authors.initials: HH
authors.lastname: Le
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742.
authors.forename: Monika
authors.initials: M
authors.lastname: Looney
authors.affiliation: Center for Advanced Study of Language, University of Maryland, College Park, MD 20742.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Strauss
authors.affiliation: Center for Advanced Study of Language, University of Maryland, College Park, MD 20742.
authors.forename: Michael
authors.initials: M
authors.lastname: Bloodgood
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742 amjose@umd.edu.
authors.forename: Antony M
authors.identifier: 0000-0003-1405-0618
authors.initials: AM
authors.lastname: Jose
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002455:Cell Division; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development; D020868:Gene Silencing; D056426:Genetic Loci; D007422:Intestines / Q000166:cytology; D007814:Larva / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009928:Organ Specificity; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D017384:Sequence Deletion; D019076:Transgenes; D015053:Zygote / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D012330:RNA, Double-Stranded