TY - JOUR
T1 - An Abundant Class of Non-coding DNA Can Prevent Stochastic Gene Silencing in the C. elegans Germline
AU - Frøkjær-Jensen, Christian
AU - Jain, Nimit
AU - Hansen, Loren
AU - Davis, M Wayne
AU - Li, Yongbin
AU - Zhao, Di
AU - Rebora, Karine
AU - Millet, Jonathan R R M
AU - Liu, Xiao
AU - Kim, Stuart K
AU - Dupuy, Denis
AU - Jorgensen, Erik M
AU - Fire, Andrew Z.
PY - 2016/7/14
Y1 - 2016/7/14
N2 - Cells benefit from silencing foreign genetic elements but must simultaneously avoid inactivating endogenous genes. Although chromatin modifications and RNAs contribute to maintenance of silenced states, the establishment of silenced regions will inevitably reflect underlying DNA sequence and/or structure. Here, we demonstrate that a pervasive non-coding DNA feature in Caenorhabditis elegans, characterized by 10-base pair periodic An/Tn-clusters (PATCs), can license transgenes for germline expression within repressive chromatin domains. Transgenes containing natural or synthetic PATCs are resistant to position effect variegation and stochastic silencing in the germline. Among endogenous genes, intron length and PATC-character undergo dramatic changes as orthologs move from active to repressive chromatin over evolutionary time, indicating a dynamic character to the An/Tn periodicity. We propose that PATCs form the basis of a cellular immune system, identifying certain endogenous genes in heterochromatic contexts as privileged while foreign DNA can be suppressed with no requirement for a cellular memory of prior exposure.
AB - Cells benefit from silencing foreign genetic elements but must simultaneously avoid inactivating endogenous genes. Although chromatin modifications and RNAs contribute to maintenance of silenced states, the establishment of silenced regions will inevitably reflect underlying DNA sequence and/or structure. Here, we demonstrate that a pervasive non-coding DNA feature in Caenorhabditis elegans, characterized by 10-base pair periodic An/Tn-clusters (PATCs), can license transgenes for germline expression within repressive chromatin domains. Transgenes containing natural or synthetic PATCs are resistant to position effect variegation and stochastic silencing in the germline. Among endogenous genes, intron length and PATC-character undergo dramatic changes as orthologs move from active to repressive chromatin over evolutionary time, indicating a dynamic character to the An/Tn periodicity. We propose that PATCs form the basis of a cellular immune system, identifying certain endogenous genes in heterochromatic contexts as privileged while foreign DNA can be suppressed with no requirement for a cellular memory of prior exposure.
U2 - 10.1016/j.cell.2016.05.072
DO - 10.1016/j.cell.2016.05.072
M3 - Journal article
C2 - 27374334
AN - SCOPUS:84978413978
SN - 0092-8674
VL - 166
SP - 343
EP - 357
JO - Cell
JF - Cell
IS - 2
ER -