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The RING finger/B-Box factor TAM-1 and a retinoblastoma-like protein LIN-35 modulate context-dependent gene silencing in Caenorhabditis elegans

Hsieh, Jenny and Liu, Jing and Kostas, Stephen A. and Chang, Chieh and Sternberg, Paul W. and Fire, Andrew (1999) The RING finger/B-Box factor TAM-1 and a retinoblastoma-like protein LIN-35 modulate context-dependent gene silencing in Caenorhabditis elegans. Genes and Development, 13 (22). pp. 2958-2970. ISSN 0890-9369. PMCID PMC317160.

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Context-dependent gene silencing is used by many organisms to stably modulate gene activity for large chromosomal regions. We have used tandem array transgenes as a model substrate in a screen for Caenorhabditis elegans mutants that affect context-dependent gene silencing in somatic tissues. This screen yielded multiple alleles of a previously uncharacterized gene, designated tam-1 (fortandem-array-modifier). Loss-of-function mutations in tam-1 led to a dramatic reduction in the activity of numerous highly repeated transgenes. These effects were apparently context dependent, as nonrepetitive transgenes retained activity in a tam-1 mutant background. In addition to the dramatic alterations in transgene activity, tam-1 mutants showed modest alterations in expression of a subset of endogenous cellular genes. These effects include genetic interactions that place tam-1 into a group called the class B synMuv genes (for aSynthetic Multivulva phenotype); this family plays a negative role in the regulation of RAS pathway activity in C. elegans. Loss-of-function mutants in other members of the class-B synMuv family, including lin-35, which encodes a protein similar to the tumor suppressor Rb, exhibit a hypersilencing in somatic transgenes similar to that of tam-1 mutants. Molecular analysis reveals that tam-1 encodes a broadly expressed nuclear protein with RING finger and B-box motifs.

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Sternberg, Paul W.0000-0002-7699-0173
Additional Information:© 1999 by Cold Spring Harbor Laboratory Press. Received June 30 1999; revised version accepted September 28 1999. We thank K. Liu, S. Parrish, B. Kelly, L. Timmons, J. Goodliffe, C. Lee, C. Ceol, E. Davison, B. Horvitz, M. Bellini, V. Guacci, P. McGee, E. Jorgensen, and A. Shearn for help and advice; M. Edgley, D. Riddle, H. Hutter, L. Huang, J. DeModena, S. Xu, J. Fleenor, J. Mendel, Y. Kohara, and K. Dej for useful materials; and R. Feldman for isolating several tam-1 alleles. This work was supported by U.S. Public Health Service grants GM37706 (A.F.); HD23690 (P.W.S.); T32GM07231 (J.H., S.K.); GM07616 (J.L., C.C.); and by the Carnegie Institution of Washington. P.W.S. is an investigator of the Howard Hughes Medical Institute. Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is supported by National Institutes of Health's National Center for Research Resources. The publication costs of this article were defrayed in part by payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 USC section 1734 solely to indicate this fact.
Funding AgencyGrant Number
NIH Predoctoral FellowshipT32GM07231
Carnegie Institution of WashingtonUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:TAM-1; Chromatin Silencing; RING finger; C. elegans; Rb; RAS Pathway
Issue or Number:22
PubMed Central ID:PMC317160
Record Number:CaltechAUTHORS:20190514-110944071
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95486
Deposited By: Tony Diaz
Deposited On:14 May 2019 20:47
Last Modified:03 Oct 2019 21:13

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