The small ubiquitin-like modifier (SUMO) is required for gonadal and uterine-vulval morphogenesis in Caenorhabditis elegans

Abstract

The small ubiquitin-like modifier (SUMO) modification alters the subcellular distribution and function of its substrates. Here we show the major role of SUMO during the development of the Caenorhabditis elegans reproductive system. smo-1 deletion mutants develop into sterile adults with abnormal somatic gonad, germ line, and vulva. SMO-1ϻGFP reporter is highly expressed in the somatic reproductive system. smo-1 animals lack a vulval-uterine connection as a result of impaired ventral uterine -cell differentiation and anchor cell fusion. Mutations in the LIN-11 LIM domain transcription factor lead to a uterine phenotype that resembles the smo-1 phenotype. LIN-11 is sumoylated, and its sumoylation is required for its activity during uterine morphogenesis. Expression of a SUMO-modified LIN-11 in the smo-1 background partially rescued -cell differentiation and retained LIN-11 in nuclear bodies. Thus, our results identify the reproductive system as the major SUMO target during postembryonic development and highlight LIN-11 as a physiological substrate whose sumoylation is associated with the formation of a functional vulval-uterine connection.[Keywords: SUMO; somatic gonad; Supplemental material is available at http://www.genesdev.org. (Schwarz et al. 1998). SUMO conjugation has been shown to affect subcellular localization of the modified substrate, thereby affecting its activity and stability (Matunis et al. 1996;Mahajan et al. 1997; Muller at al. 1998). Several transcription factors are modified by sumoylation. Whereas SUMO modification negatively regulates the androgen receptor, SP3, c-Jun, and p53 (Gostissa et al. 1999; Muller et al. 2000;Poukka et al. 2000;Schmidt and Muller 2002), sumoylation of the glucocorticoid receptor increases its transcriptional activities (LeDrean et al. 2002). Sumoylation also affects transcriptional activities indirectly. For example, SUMO conjugation to class II histone deacetylase impairs its transcription-repressing function (Kirsch et al. 2002). Alternatively, sumoylation has also been shown to affect nuclear and subnuclear (nucleolar or PML nuclear body) localization of regulatory proteins primarily implicated in transcriptional control (Sternsdorf et al. 1997;Pichler et al. 2002).The SUMO conjugation system is essential for viability in Saccharomyces cerevisiae (Melchoir 2000). Phenotypes observed upon aberrant sumoylation in S. cerevisiae include impaired septin ring formation, chromosomal segregation, and progression of the cell cycle through G 2 -M (Johnson and Blobel 1999). Studies in Arabidopsis suggest that the SUMO conjugation system has a role in protection against stress and/or repair of stressrelated damage (Kurepa et al. 2002). In Drosophila melanogaster, the loss-of-function mutation of semushi, the UBC9 (SUMO-conjugating enzyme) ortholog, prevents nuclear import of the transcription factor Bicoid (Bcd) and results in impaired embryogenesis (Epps and Tanda 1998).

MafG Sumoylation Is Required for Active Transcriptional Repression

“…However, most of the previous work was performed using transient overexpression in cultured cells, and thus, the biological significance of those phenomena was not entirely clear. Two genetic studies with Caenorhabditis elegans have demonstrated that the sumoylation of polycomb group proteins is essential for their physiological repression of Hox genes (39) and that the sumoylation of LIN-11, a LIM homeobox protein, is important for its function in uterine/vulval morphogenesis (2). To address the basic mechanistic concern regarding the in vivo consequences of sumoylation, the status of sumoylation was examined in mice.…”

Sumoylation of LIN-1 promotes transcriptional repression and inhibition of vulval cell fates

“…Only a small fraction of steady-state LIN-1 was post-translationally modified by SUMO. It is possible that sumoylation is a stable modification of a small fraction of LIN- (Broday et al, 2004) observed a similar defect. Second, we used RNA interference (RNAi) to reduce the levels of smo-1 RNA by feeding hermaphrodites E. coli that express doublestranded smo-1 RNA.…”

SUMO Modification Regulates MafB-Driven Macrophage Differentiation by Enabling Myb-Dependent Transcriptional Repression

“…Although in most cases these effects were observed only in transient-transactivation assays and biological consequences were not investigated or could not be detected (10), transgenic studies also implicate SUMO modification in transcriptional repression (34). Gain-of-function experiments in Caenorhabditis elegans (6) and Xenopus laevis (46) further suggest that SUMO modification can also modulate transcription factor activity in developmental processes. Generally, however, little is known about the biological significance of transcription factor SUMO modification in higher vertebrates and particularly its role in controlling the combinatorial action of transcription factors.…”