| Study (year, journal) with URL | Biological context | Key findings about LIN-65 molecular function/interactions | Localization/structures | Quantitative data reported | Evidence type |
|---|---|---|---|---|---|
| Ceol et al. 2006, *Genetics* — https://doi.org/10.1534/genetics.106.056465 | Vulval development; antagonism of let-60/Ras signaling; synMuv classification | Positional cloning, RNAi, cDNA rescue, and allele sequencing identified **Y71G12B.9 as lin-65** and placed **lin-65** in the **synMuvB/class B** pathway that antagonizes Ras signaling. Heat-shock-driven expression of the 728-aa cDNA rescued the Muv phenotype; allele behavior resembled other class B synMuv genes. Mutations in **lin-65** altered vulval fate patterns and genetically interacted with sensitized backgrounds that reveal synMuv function (pqac-00000008, pqac-00000009, pqac-00000010, pqac-00000012, pqac-00000014). | Encodes a predicted **728-aa protein** from Y71G12B.9; no domain family assigned in this paper. Molecular lesions included **W534amber truncations** in **n3441/n3541** and **S720L** in **n3543** (pqac-00000008, pqac-00000009, pqac-00000011). | Reported rescue in **2 transgenic lines**; specific vulval fate scores included values such as **3.0 (60, 35)** in suppression assays and P8.p fate frequencies including **45 (31)** in one assay table; allele mapping localized lin-65 between **Y71G12B.17 and Y71G12B.18** (pqac-00000008, pqac-00000009, pqac-00000010, pqac-00000012). | Positional mapping, RNAi phenocopy, cDNA rescue, mutant allele sequencing, vulval fate scoring, genetic interaction analysis |
| Tian et al. 2016, *Cell* — https://doi.org/10.1016/j.cell.2016.04.011 | Mitochondrial stress response and longevity; UPRmt | **lin-65** is required for mitochondrial stress–induced chromatin reorganization and for full **UPRmt** activation. LIN-65 functions with **MET-2** in stress-dependent H3K9me2 remodeling; LIN-65 and **DVE-1** show interdependent nuclear accumulation. Loss of lin-65 suppresses induction of the **hsp-6p::gfp** UPRmt reporter (pqac-00000003, pqac-00000005, pqac-00000023). | A **lin-65p::lin-65::mCherry** reporter was diffuse/cytosolic under control conditions but accumulated in **intestinal nuclei** after **cco-1 RNAi**; this stress-induced nuclear accumulation required **met-2** (pqac-00000003, pqac-00000023). | EMS screen covered **2,400 mutagenized genomes** and identified **16 suppressor mutants**; **uth2** was mapped to **lin-65** with a **Glu367Lys** substitution. Immunoblot and reporter imaging showed strong suppression of **hsp-6p::gfp** induction in **lin-65(n3441)**, similar to **atfs-1** loss (pqac-00000003, pqac-00000023). | EMS suppressor screen, whole-genome sequencing, reporter imaging, Western blot, transgenic localization imaging, RNAi stress induction |
| Mutlu et al. 2018, *Science Advances* — https://doi.org/10.1126/sciadv.aat6224 | Timing of embryonic heterochromatin formation | LIN-65 is a **MET-2 binding partner** that is **rate-limiting** for embryonic **H3K9me2** deposition and for **MET-2 nuclear accumulation**. The study proposed that MET-2, LIN-65, and ARLE-14 accumulate in nuclei as embryos mature and form nuclear hubs that initiate heterochromatin formation (pqac-00000006, pqac-00000020). | LIN-65 is initially more **cytosolic** in early embryos and later accumulates into **nuclear hubs** with MET-2 and ARLE-14. Predicted architecture: extensive **disordered regions**, a **high-probability coiled-coil**, and a **C-terminal β-sandwich fold**; functionally compared to mammalian **ATF7IP**, possibly by convergent evolution (pqac-00000006, pqac-00000020). | The paper quantified altered **MET-2::GFP nuclear intensity** in **lin-65** mutants and showed dosage sensitivity from **lin-65(+/−)** mothers affecting H3K9 methylation timing, though the excerpt does not provide all numeric values (pqac-00000006, pqac-00000020). | Proteomics, endogenous imaging, line-scan quantification, embryonic staging, mutant analysis |
| Delaney et al. 2019, *Journal of Cell Biology* — https://doi.org/10.1083/jcb.201811038 | Heterochromatin foci formation, transcriptional repression, perinuclear anchoring, stress resistance | LIN-65 is a **highly unstructured/disordered cofactor** that physically binds **MET-2/SETDB1** and **ARLE-14**. It is required for **MET-2 localization/stability**, **heterochromatic focus formation**, **H3K9me2 deposition**, transcriptional repression of repeats and developmental genes, and **perinuclear anchoring** of heterochromatin. LIN-65 is proposed as a functional analog of **ATF7IP/MCAF1** and may have some MET-2-independent roles (pqac-00000000, pqac-00000001, pqac-00000002, pqac-00000004, pqac-00000016, pqac-00000017, pqac-00000021). | LIN-65 colocalizes with MET-2 and ARLE-14 in **dynamic perinuclear nuclear foci**. Predicted to be ~**70% low-complexity/unstructured**, with **two long unstructured stretches**, a short **coiled-coil**, and a **folded C-terminal domain**. Foci are sensitive to **1,6-hexanediol**, consistent with condensate/phase-separation-like behavior (pqac-00000000, pqac-00000007, pqac-00000018). | Reciprocal pulldowns recovered **MET-2 and ARLE-14** as the major LIN-65 interactors. Colocalization: **Pearson r = 0.65** for LIN-65 with MET-2, **r = 0.74** for ARLE-14; MET-2 with H3K9me2 **r = 0.7**. In **lin-65** mutants, nuclear MET-2 dropped from **4.5 ± 0.8** to **2.5 ± 0.4** fold/background, cytoplasmic MET-2 rose from **1.6 ± 0.2** to **2.2 ± 0.3**, and MET-2 protein fell by **~40–50%**. Satellite repeat derepression was **~55%** of the level seen in **met-2** mutants. MET-2 FRAP **t1/2 ≈ 2.64 s**. Heat-shock hatching: wild type **80 ± 14%**, **met-2 31 ± 10%**, **lin-65 48 ± 5%**. Misregulated genes in **lin-65** vs **met-2** showed **Pearson = 0.7** overlap (pqac-00000000, pqac-00000001, pqac-00000004, pqac-00000007, pqac-00000017, pqac-00000018, pqac-00000019). | Endogenous FLAG pulldown LC-MS/MS, reciprocal immunoprecipitation, confocal imaging, FRAP, 1,6-hexanediol sensitivity, RNAi, reporter derepression, transcriptomics, stress assays |
| Jash & Csankovszki 2024, *DNA* review — https://doi.org/10.3390/dna4010004 | Review of early embryonic chromatin organization in *C. elegans* | The review synthesizes the field’s understanding that LIN-65 is an **unstructured MET-2/SETDB1 cofactor** needed for heterochromatic foci and repression, and that regulated **MET-2 nuclear accumulation** helps time heterochromatin establishment in embryos. It also places LIN-65-linked H3K9 methylation pathways in the context of **perinuclear heterochromatin positioning** (pqac-00000022). | Described at the review level as an **unstructured cofactor** associated with MET-2 nuclear foci and embryonic chromatin organization; no new localization experiments reported in the review excerpt (pqac-00000022). | No new primary quantitative measurements in the cited excerpt; the review summarizes prior studies rather than reporting new assays (pqac-00000022). | Narrative review of primary literature |
| Sands et al. 2024, *bioRxiv* preprint — https://doi.org/10.1101/2024.01.22.576748 | Maternal H3K9 methyltransferases and somatic monoallelic expression (MAE) | Preprint proposes that **MET-2/SETDB1 works with LIN-65/ATF7IP-like and ARLE-14** to **prevent monoallelic expression**. LIN-65 is described as helping MET-2 bind in the cytoplasm and **translocate to the nucleus**. In reporter assays, **lin-65(RNAi)** caused a strong increase in MAE, visually resembling **met-2** loss (pqac-00000025, pqac-00000026). | LIN-65 is discussed functionally as an upstream factor for **MET-2 nuclear translocation**; no new structural mapping beyond its ATF7IP-like role in the provided excerpt (pqac-00000025, pqac-00000026). | RNAi in **hsp-90 reporter allele strains** showed a **significant increase in MAE/intrinsic noise** with **lin-65(RNAi)**; the excerpt does not provide exact numeric effect sizes or p-values. The model places action in the **intestinal progenitor E cell of 8-cell embryos** (pqac-00000025, pqac-00000026). | Reporter assays, RNAi knockdown, developmental genetics/model building |


*Table: This table summarizes the main experimental evidence for C. elegans LIN-65/Y71G12B.9 across landmark and recent studies, covering Ras/synMuv biology, UPRmt, embryonic heterochromatin, and emerging 2024 models. It is useful as a quick evidence map linking function, localization, structure, and assay types to specific publications.*