Caenorhabditis elegans mtf-1 encodes matefin, which has a predicted SUN domain, a coiled-coil region, an anti-erbB-2 IgG domain, and two hydrophobic regions. We show that matefin is a nuclear membrane protein that colocalizes in vivo with Ce-lamin, the single nuclear lamin protein in C. elegans, and binds Ce-lamin in vitro but does not require Ce-lamin for its localization. Matefin is detected in all embryonic cells until midembryogenesis and thereafter only in germ-line cells. Embryonic matefin is maternally deposited, and matefin is the first nuclear membrane protein known to have germ line-restricted expression. Animals homozygous for an mtf-1 deletion allele show that matefin is essential for germ line maturation and survival. However, matefin is also required for embryogenesis because mtf-1 (RNAi) embryos die around the Ϸ300-cell stage with defects in nuclear structure, DNA content, and chromatin morphology. Down-regulating matefin in mes-3 animals only slightly enhances embryonic lethality, and elimination of UNC-84, the only other SUN-domain gene in C. elegans, has no affect on mtf-1 (RNAi) animals. Thus, mtf-1 mediates a previously uncharacterized pathway(s) required for embryogenesis as well as germ line proliferation or survival. Lamins are nuclear intermediate filament proteins found in metazoan cells at the nuclear periphery and in the nucleoplasm (1). Lamins interact with most known inner nuclear membrane proteins as well as with several nucleoplasmic proteins (2). Nuclear architecture, cell cycle progression, DNA replication, and RNA transcription and splicing all depend on lamins (3, 4). Consistent with such roles, many of these laminbinding proteins also bind transcription repressors and chromatin proteins.To understand nuclear lamins and lamin-associated protein functions in vivo we turned to Caenorhabditis elegans, studying its single lamin protein, Ce-lamin (5), and three inner nuclear membrane proteins, Ce-emerin, Ce-MAN1 (5, 6), and UNC-84 (7). UNC-84 contains an Ϸ120-residue SUN (Sad1p-UNC-84 homology) domain (8) with an unknown function. The SUN domain is also found in four human proteins, two of which localize at the nuclear envelope (9). UNC-84 is expressed in most C. elegans cells, and it depends on Ce-lamin for its nuclearenvelope localization (7). However, mutations in unc-84 cause nuclear migration or nuclear anchoring defects in only a subset of cells, leading to uncoordinated movement (8). At least two nuclear-envelope proteins, UNC-83 and ANC-1, require the SUN domain of UNC-84 for their nuclear-envelope localization and ability to regulate nuclear position (10). To explain their nuclear-envelope anchoring, a ''bridging model'' was proposed in which the transmembrane domains of UNC-83 and ANC-1 cross the outer nuclear membrane (ONM), and their luminal domains interact with the luminal domain of UNC-84 embedded in the inner nuclear membrane (7, 10).Based on the hypothesis that the SUN domain defined a new family of nuclear-envelope proteins, we searched the C. elegans genome for ot...

Barrier to autointegration factor (BAF) binds double-stranded DNA, selected histones, transcription regulators, lamins, and LAP2–emerin–MAN1 (LEM) domain proteins. During early Caenorhabditis elegans embryogenesis, BAF-1 is required to organize chromatin, capture segregated chromosomes within the nascent nuclear envelope, and assemble lamin and LEM domain proteins in reforming nuclei. In this study, we used C. elegans with a homozygous deletion of the baf-1 gene, which survives embryogenesis and larval stages, to report that BAF-1 regulates maturation and survival of the germline, cell migration, vulva formation, and the timing of seam cell fusion. In the seam cells, BAF-1 represses the expression of the EFF-1 fusogen protein, but fusion still occurs in C. elegans lacking both baf-1 and eff-1. This suggests the existence of an eff-1–independent mechanism for cell fusion. BAF-1 is also required to maintain the integrity of specific body wall muscles in adult animals, directly implicating BAF in the mechanism of human muscular dystrophies (laminopathies) caused by mutations in the BAF-binding proteins emerin and lamin A.

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The haplotypes of Y chromosome (paternally inherited) and mtDNA (maternally inherited) were analyzed in representatives of six Jewish communities (Ashkenazic, North African, Near Eastern, Yemenite, Minor Asian/Balkanian, and Ethiopian). For both elements, the Ethiopian community has a mixture of typically African and typically Caucasian haplotypes and is significantly different from all others. The other communities, whose haplotypes are mostly Caucasian, are more closely related; significant differences that were found among some of them possibly indicate the effects of admixture with neighboring communities of non-Jews. The different contribution of the Y chromosome and mtDNA haplotypes to the significant differences among the communities can be explained by unequal involvement of males and females in the different admixtures. In all communities, except the Ethiopians, the level of diversity (h) for Y chromosome haplotypes is higher than that for mtDNA haplotypes, suggesting that in each community the people who become parents include more males than females. An opposite proportion (more females than males) is found among the Ethiopians.