RRC ID 53305
Author Le HH, Looney M, Strauss B, Bloodgood M, Jose AM.
Title Tissue homogeneity requires inhibition of unequal gene silencing during development.
Journal J. Cell Biol.
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.
Volume 214(3)
Pages 319-31
Published 2016-8-1
DOI 10.1083/jcb.201601050
PII jcb.201601050
PMID 27458132
PMC PMC4970325
MeSH Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / embryology* Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / metabolism Cell Division Embryo, Nonmammalian / cytology Embryo, Nonmammalian / metabolism Embryonic Development* Gene Silencing* Genetic Loci Intestines / cytology Larva / metabolism Nucleic Acid Conformation Organ Specificity* RNA Interference RNA, Double-Stranded / chemistry RNA, Double-Stranded / metabolism Repetitive Sequences, Nucleic Acid / genetics* Sequence Deletion Transgenes Zygote / metabolism
IF 8.891
Times Cited 3
C.elegans tm1116