Intergenerational Transmission of Gene Regulatory Information in Caenorhabditis elegans

Abstract

Epigenetic mechanisms can stably maintain gene expression states even after the initiating conditions have changed. Often epigenetic information is transmitted only to daughter cells, but evidence is emerging, in both vertebrate and invertebrate systems, for transgenerational epigenetic inheritance (TEI), the transmission of epigenetic gene regulatory information across generations. Each new description of TEI helps uncover the properties, molecular mechanisms and biological roles for TEI. The nematode Caenorhabditis elegans has been particularly instrumental in the effort to understand TEI, as multiple environmental and genetic triggers can initiate an epigenetic signal that can alter the expression of both transgenes and endogenous loci. Here, we review recent studies of TEI in C. elegans.

Keywords: Caenorhabditis elegans; HRDE-1; epigenetic; nuclear RNAi; transgenerational.

Figure 1

In C. elegans, piRNAs are transcribed by RNA Polymerase II (Pol II) and primary siRNAs can be produced from exogenous dsRNA. piRNAs and primary siRNAs are stabilized by unique Argonaute proteins (yellow) and can direct the production of highly amplified secondary siRNAs by RNA-directed RNA polymerases (RdRPs). Secondary siRNAs bound to the Argonaute HRDE-1 can direct transcriptional and post-transcriptional silencing of homologous loci. HRDE-1 is required for the heritable transmission of gene regulatory information in C. elegans.

Figure 2

A summary of transgenerational epigenetic inheritance in C. elegans. A. Epigenetic silencing of transgenes and endogenous loci can be initiated by exogenous RNA, endogenous piRNAs, and a multi-copy intergenic region. Silencing persists after loss of the initiating trigger in the germline (black bars) or soma (blue bars). Bars represent transmission efficiency at each generation. B. Gene expression and physiological changes initiated by an environmental stress or methyltransferase inactivity can be persist transgenerationally. C. Key for parts A and B. ND: Not determined. N/A: Not applicable.

Figure 3

sid-1 TEI as a model of RNA mediated inheritance. (1) Amplified siRNAs transcribed from a multicopy sid-1-promoter transgene array (2) target rare sid-1 pre-mRNA and (3) prime the RdRP dependent spread and amplification of siRNA targeting the sid-1 coding region prior to mRNA trans-splicing. (4) siRNA targeting the coding region are maintained by an RdRP-dependent autocatalytic amplification cycle. Mother to progeny transfer of silencing is accomplished by transfer of germline siRNA via ooctyes. (5) PTGS-produced germline siRNA are transmitted to oocytes. (6) siRNA persist in embryonic germline precursor (pink) and initiate nuclear TGS to silence sid-1 in somatic cells (blue). (7) PTGS silencing is maintaned and silences sid-1 in the cytoplasm of the developing germline.