Os02g0232100
HEI10 exerts its effects in the recombination process through modification of diverse meiotic components during rice meiosis.
Contents
Annotated Information
HEI10 exerts its effects in the recombination process through modification of diverse meiotic components during rice meiosis.
Function
Human Enhancer of Invasion 10 (HEI10; also known asCCNB1IP1) was first isolated from humans and it was demonstrated that the molecule played a role in the mitotic cell cycle [1]. HEI10 functions as an E3 Ubiquitin ligase to regulate cell migration and invasion [1][2]. Further studies in mice revealed that mutation of HEI10 led to dramatic meiosis defects, indicating an important role of HEI10 during meiosis. It was shown in mice that mutation of HEI10 resulted in high prevalence of univalent chromosomes during metaphase I, which finally leads to a sterile phenotype. Furthermore, results obtained in experiments using a yeast two-hybrid system suggest a function for HEI10 as E3 SUMO ligase in addition to the ubiquitin ligase role reported in somatic cells[2].It is further known that HEI10 is required for meiotic CO formation. Consistent with this, it suggests that the role of HEI10 in rice might be the homolog of budding yeast Zip3 and C. elegans ZHP-3. Those genes may play both conserved and divergent roles in homologous recombination in their respective species. It suggests that also in rice HEI10 is essential for reciprocal recombination between homologous chromosomes[3].
Mutation
60Co γ-ray irradiation was used to induce a sterile mutant from the japonica rice variety Wuxiangjing 9.The mutant showed normal vegetative growth but exhibited complete sterility (Figure 1A and 1B). Cytological observation of anthers showed that almost all pollens were shrunken and inviable (Figure 1C and 1D). When pollinated with wild-type (WT) pollens, the mutant spikelets were unable to set any seeds, suggesting that the female gametes were also sterile. The progenies of the heterozygous plants segregated from normal to sterile phenotype in a 3:1 ratio (fertile, 30; sterile, 10), indicating that a single recessive gene is responsible for the sterile phenotype[3].
Expression（Mutant VS Wild type）
Using sterile plants that segregated in F2 and F3 populations, the gene was mapped on the long arm of rice chromosome 2, which was further narrowed to a 100-kb region. All genes within this region were amplified and sequenced. A single nucleotide G to A substitution was found at position 140 of the first exon of the Os02g0232100 gene (Figure 2). This substitution introduced a new translation initiation site (ATG) in the 5’-UTR, which would theoretically express a totally different peptide[3]. The hei10 mutant chromosomes behaved normally during leptotene and zygotene. Fully aligned chromosomes were detected during pachytene (Figure 3A). However, during diakinesis, the mutant cells showed a mixture of both univalent and bivalent chromosomes (Figure 3B). At metaphase I, the bivalents aligned well on the equatorial plate while some of the univalents were scattered in the nucleus (Figure 3C). In anaphase I, the bivalents separated normally but the scattered univalents segregated randomly. Besides those randomly distributed univalents, many univalents also aligned on the equatorial plate in metaphase I (Figure 3D) and underwent precocious separation of sister chromatids in anaphase I (Figure 3E), indicating a bipolar orientation of sister kinetochores. In telophase I and prophase II, an uneven number of chromosomes was observed in the two related cells. After the second division, tetrads with aberrant numbers of chromosomes were formed. In addition, multiple micronuclei were frequently observed (Figure 3F) [3]. To accurately define the spatial and temporal distribution of HEI10 during meiosis in rice, dual immunolocalization experiments were performed using polyclonal antibodies against REC8 and HEI10 protein, raised in rabbit and mouse, respectively. To obtain the precise localization of HEI10 bright foci on the chromosome, observation of scattered chromosomes at late pachytene revealed that one, two or three, frequently two, prominent foci localized on each pair of homologs (Figure 4A). Additionally, when two or three foci occurred on the same chromosome, they tended to be spaced far apart. Immunostaining using antibodies against HEI10 and CENH3 also revealed that about 95.6% HEI10 foci located outside CENH3 position at late pachytene (Figure 4B). To further explore whether those HEI10 bright foci were randomly distributed along bivalents, we measured the interfocus distance among bright HEI10 focus on the shortest chromosome of the cell and estimated the existence of interference using the interference parameter n of the gamma model[4][5] (Figure 4D). The result showed that HEI10 bright foci on a single chromosome displayed strong interference[3].
Evolution
HEI10 is the most likely ortholog of ZHP-3 and Zip3 in rice, although other proteins belonging to the Zip3 family cannot be excluded. In contrast to Zip3, both HEI10 and ZHP-3 exhibit a similar dynamic localization pattern, implying that the proteins may evolve new functions during meiotic recombination in multicellular organism. In C. elegans ZHP-3 was required for SC asymmetrical disassembly and normal bivalent structure [6]. Such defects were not observed in rice, implying probable diversification of Zip3 homologs even among multicelluar organisms.
Knowledge Extension
In hei10 mutants, only about 31% chiasmata were maintained. This number is similar to that of mer3 mutants, in which about 28% chiasmata were remained. Previous studies revealed that there are at least two classes of CO which occur in budding yeast and Arabidopsis [7][8][9]. Investigations of mer3 mutants in rice showed that apart from a reduced number of chiasmata, the remaining chiasmata distributed randomly among cells, suggesting that rice might also have at least two kinds of COs: one that appears to be sensitive to interference, whereas the other one is not [10]. The close number of residual chiasmata indicates similar contributions of HEI10 and MER3 during CO formation. Considering the close number and similar random distribution of residual chiasmata noted in mer3 and hei10 mutants, it is likely that HEI10 and MER3 may act in the same CO pathway, namely an interference-sensitive pathway.Besides a reduced chiasma frequency, hei10 also showed a precocious segregation of sister chromatids of some univalents at anaphase I.
Labs working on this gene
- State Key Laboratory of Plant Genomics and Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing,China.
- Biotechnology Research Institute/National Key Facility for Gene Resources and Gene Improvement, Chinese Academy of Agricultural Sciences, Beijing, China.
References
- ↑ 1.0 1.1 Toby GG, Gherraby W, Coleman TR, Golemis EA (2003) A novel RING finger protein, human enhancer of invasion 10, alters mitotic progression through regulation of cyclin B levels. Mol Cell Biol 23: 2109–2122.
- ↑ 2.0 2.1 Singh MK, Nicolas E, Gherraby W, Dadke D, Lessin S, et al. (2007) HEI10 negatively regulates cell invasion by inhibiting cyclin B/Cdk1 and other promotility proteins. Oncogene 26: 4825–4832.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Wang, K., Wang, M., Tang, D., Shen, Y., Miao, C., Hu, Q., ... & Cheng, Z. (2012).The role of rice HEI10 in the formation of meiotic crossovers. PLoS genetics, 8(7), e1002809.
- ↑ de Boer E, Stam P, Dietrich AJ, Pastink A, Heyting C (2006) Two levels of interference in mouse meiotic recombination. Proc Natl Acad Sci U S A 103: 9607–9612.
- ↑ Lhuissier FG, Offenberg HH, Wittich PE, Vischer NO, Heyting C (2007) The mismatch repair protein MLH1 marks a subset of strongly interfering crossovers in tomato. Plant Cell 19: 862–876.
- ↑ Bhalla N, Wynne DJ, Jantsch V, Dernburg AF (2008) ZHP-3 acts at crossovers to couple meiotic recombination with synaptonemal complex disassembly and bivalent formation in C. elegans. PLoS Genet 4: e1000235.
- ↑ Borner GV, Kleckner N, Hunter N (2004) Crossover/noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell 117: 29–45.
- ↑ Mercier R, Jolivet S, Vezon D, Huppe E, Chelysheva L, et al. (2005) Two meiotic crossover classes cohabit in Arabidopsis: one is dependent on MER3, whereas the other one is not. Curr Biol 15: 692–701.
- ↑ Higgins JD, Armstrong SJ, Franklin FC, Jones GH (2004) The Arabidopsis MutS homolog AtMSH4 functions at an early step in recombination: evidence for two classes of recombination in Arabidopsis. Genes & Dev 18: 2557–2570.
- ↑ Wang K, Tang D, Wang M, Lu J, Yu H, et al. (2009) MER3 is required for normal meiotic crossover formation, but not for presynaptic alignment in rice. J Cell Sci 122: 2055–2063.
