The C. elegans dosage compensation complex mediates interphase X chromosome compaction

Abstract Background Dosage compensation is a specialized gene regulatory mechanism which equalizes X-linked gene expression between sexes. In Caenorhabditis elegans, dosage compensation is achieved by the activity of the dosage compensation complex (DCC). The DCC localizes to both X chromosomes in hermaphrodites to downregulate gene expression by half. The DCC contains a subcomplex (condensin IDC) similar to the evolutionarily conserved condensin complexes which play fundamental roles in chromosome dynamics during mitosis and meiosis. Therefore, mechanisms related to mitotic chromosome condensation have been long hypothesized to mediate dosage compensation. However experimental evidence was lacking. Results Using 3D FISH microscopy to measure the volumes of X and chromosome I territories and to measure distances between individual loci, we show that hermaphrodite worms deficient in DCC proteins have enlarged interphase X chromosomes when compared to wild type. By contrast, chromosome I is unaffected. Interestingly, hermaphrodite worms depleted of condensin I or II show no phenotype. Therefore X chromosome compaction is specific to condensin IDC. In addition, we show that SET-1, SET-4, and SIR-2.1, histone modifiers whose activity is regulated by the DCC, need to be present for the compaction of the X chromosome territory. Conclusion These results support the idea that condensin IDC, and the histone modifications regulated by the DCC, mediate interphase X chromosome compaction. Our results link condensin-mediated chromosome compaction, an activity connected to mitotic chromosome condensation, to chromosome-wide repression of gene expression in interphase.http://deepblue.lib.umich.edu/bitstream/2027.42/109510/1/13072_2014_Article_335.pd

Crossing over is coupled to late meiotic prophase bivalent differentiation through asymmetric disassembly of the SC

Homologous chromosome pairs (bivalents) undergo restructuring during meiotic prophase to convert a configuration that promotes crossover recombination into one that promotes bipolar spindle attachment and localized cohesion loss. We have imaged remodeling of meiotic chromosome structures after pachytene exit in Caenorhabditis elegans. Chromosome shortening during diplonema is accompanied by coiling of chromosome axes and highly asymmetric departure of synaptonemal complex (SC) central region proteins SYP-1 and SYP-2, which diminish over most of the length of each desynapsing bivalent while becoming concentrated on axis segments distal to the single emerging chiasma. This and other manifestations of asymmetry along chromosomes are lost in synapsis-proficient crossover-defective mutants, which often retain SYP-1,2 along the full lengths of coiled diplotene axes. Moreover, a γ-irradiation treatment that restores crossovers in the spo-11 mutant also restores asymmetry of SYP-1 localization. We propose that crossovers or crossover precursors serve as symmetry-breaking events that promote differentiation of subregions of the bivalent by triggering asymmetric disassembly of the SC

Chromosome Painting Reveals Asynaptic Full Alignment of Homologs and HIM-8–Dependent Remodeling of X Chromosome Territories during Caenorhabditis elegans Meiosis

During early meiotic prophase, a nucleus-wide reorganization leads to sorting of chromosomes into homologous pairs and to establishing associations between homologous chromosomes along their entire lengths. Here, we investigate global features of chromosome organization during this process, using a chromosome painting method in whole-mount Caenorhabditis elegans gonads that enables visualization of whole chromosomes along their entire lengths in the context of preserved 3D nuclear architecture. First, we show that neither spatial proximity of premeiotic chromosome territories nor chromosome-specific timing is a major factor driving homolog pairing. Second, we show that synaptonemal complex-independent associations can support full lengthwise juxtaposition of homologous chromosomes. Third, we reveal a prominent elongation of chromosome territories during meiotic prophase that initiates prior to homolog association and alignment. Mutant analysis indicates that chromosome movement mediated by association of chromosome pairing centers (PCs) with mobile patches of the nuclear envelope (NE)–spanning SUN-1/ZYG-12 protein complexes is not the primary driver of territory elongation. Moreover, we identify new roles for the X chromosome PC (X-PC) and X-PC binding protein HIM-8 in promoting elongation of X chromosome territories, separable from their role(s) in mediating local stabilization of pairing and association of X chromosomes with mobile SUN-1/ZYG-12 patches. Further, we present evidence that HIM-8 functions both at and outside of PCs to mediate chromosome territory elongation. These and other data support a model in which synapsis-independent elongation of chromosome territories, driven by PC binding proteins, enables lengthwise juxtaposition of chromosomes, thereby facilitating assessment of their suitability as potential pairing partners

The pathogenesis and pathology of idiopathic pleuroparenchymal fibroelastosis

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare subtype of idiopathic interstitial pneumonias that consists of elastofibrosis involving the lung parenchyma and pleural collagenous fibrosis predominantly located in the upper lobes. IPPFE has various distinct clinical and physiological characteristics, including platythorax and a marked decrease of forced vital capacity with an increased residual volume on a respiratory function test. The concept of IPPFE is now widely recognized and some diagnostic criteria have been proposed. In addition, the accumulation of cases has revealed the pathological features of IPPFE. However, little is known about the pathogenesis or the process of disease formation in IPPFE. This review article will provide a summary of the pathological features and previously reported hypotheses on disease formation in IPPFE, to discuss the potential etiologies and pathogenesis of IPPFE

Chromosome-Wide Regulation of Meiotic Crossover Formation in Caenorhabditis elegans Requires Properly Assembled Chromosome Axes

Most sexually reproducing organisms depend on the regulated formation of crossovers, and the consequent chiasmata, to accomplish successful segregation of homologous chromosomes at the meiosis I division. A robust, chromosome-wide crossover control system limits chromosome pairs to one crossover in most meioses in the nematode Caenorhabditis elegans; this system has been proposed to rely on structural integrity of meiotic chromosome axes. Here, we test this hypothesis using a mutant, him-3(me80), that assembles reduced levels of meiosis-specific axis component HIM-3 along cohesin-containing chromosome axes. Whereas pairing, synapsis, and crossing over are eliminated when HIM-3 is absent, the him-3(me80) mutant supports assembly of synaptonemal complex protein SYP-1 along some paired chromosomes, resulting in partial competence for chiasma formation. We present both genetic and cytological evidence indicating that the him-3(me80) mutation leads to an increased incidence of meiotic products with two crossovers. These results indicate that limiting the amount of a major axis component results in a reduced capacity to communicate the presence of a (nascent) crossover and/or to discourage others in response

A Defective Meiotic Outcome of a Failure in Homologous Pairing and Synapsis Is Masked by Meiotic Quality Control.

Successful gamete production is ensured by meiotic quality control, a process in which germ cells that fail in bivalent chromosome formation are eliminated during meiotic prophase. To date, numerous meiotic mutants have been isolated in a variety of model organisms, using defects associated with a failure in bivalent formation as hallmarks of the mutant. Presumably, the meiotic quality control mechanism in those mutants is overwhelmed. In these mutants, all germ cells fail in bivalent formation, and a subset of cells seem to survive the elimination process and develop into gametes. It is possible that mutants that are partially defective in bivalent formation were missed in past genetic screens, because no evident meiotic defects associated with failure in bivalent formation would have been detectable. Meiotic quality control effectively eliminates most failed germ cells, leaving predominately successful ones. Here, we provide evidence supporting this possibility. The Caenorhabditis elegans mrg-1 loss-of-function mutant does not appear to be defective in bivalent formation in diakinesis oocytes. However, defects in homologous chromosome pairing and synapsis during the preceding meiotic prophase, prerequisites for successful bivalent formation, were observed in most, but not all, germ cells. Failed bivalent formation in the oocytes became evident once meiotic quality control was abrogated in the mrg-1 mutant. Both double-strand break repair and synapsis checkpoints are partly responsible for eliminating failed germ cells in the mrg-1 mutant. Interestingly, removal of both checkpoint activities from the mrg-1 mutant is not sufficient to completely suppress the increased germline apoptosis, suggesting the presence of a novel meiotic checkpoint mechanism