Biology subjects

Dernburg, A.

Publications and source records attributed to Dernburg, A..

5 recordsLinked to original sources

bioRxiv2022

Widespread transposon co-option in the Caenorhabditis germline regulatory network

The movement of selfish DNA elements can lead to widespread genomic alterations with potential to create novel functions. Here we show that transposon expansions in Caenorhabditis nematodes led to extensive rewiring of germline transcriptional regulation. We find that about one third of C. elegans germline-specific promoters have been co-opted from two related Miniature Inverted Repeat Transposable Elements (MITEs), CERP2 and CELE2. The promoters are regulated by HIM-17, a THAP domain-containing transcription factor related to a transposase. Expansion of CERP2 occurred prior to radiation of the Caenorhabditis genus, as did fixation of mutations in HIM-17 through positive selection, whereas CELE2 expanded only in C. elegans. Through comparative analyses in C. briggsae, we find evolutionary conservation of most CERP2 co-opted promoters, but a substantial fraction of events are species specific. Our work reveals the emergence of a novel transcriptional network driven by TE co-option with a major impact on regulatory evolution.

genomics↗

bioRxiv2021

Crossover patterning through kinase-regulated condensation and coarsening of recombination nodules

Meiotic recombination is highly regulated to ensure precise segregation of homologous chromosomes. Evidence from diverse organisms indicates that the synaptonemal complex (SC), which assembles between paired chromosomes, plays essential roles in crossover formation and patterning. Several additional "pro-crossover" proteins are also required for recombination intermediates to become crossovers. These typically form multiple foci or recombination nodules along SCs, and later accumulate at fewer, widely spaced sites. Here we report that in C. elegans CDK-2 is required to stabilize all crossover intermediates and stabilizes interactions among pro-crossover factors by phosphorylating MSH-5. Additionally, we show that the conserved RING domain proteins ZHP-3/4 diffuse along the SC and remain dynamic following their accumulation at recombination sites. Based on these and previous findings we propose a model in which recombination nodules arise through spatially restricted biomolecular condensation and then undergo a regulated coarsening process, resulting in crossover interference.

cell biology↗

bioRxiv2021

Complete genomic and epigenetic maps of human centromeres

Existing human genome assemblies have almost entirely excluded highly repetitive sequences within and near centromeres, limiting our understanding of their sequence, evolution, and essential role in chromosome segregation. Here, we present an extensive study of newly assembled peri/centromeric sequences representing 6.2% (189.9 Mb) of the first complete, telomere-to-telomere human genome assembly (T2T-CHM13). We discovered novel patterns of peri/centromeric repeat organization, variation, and evolution at both large and small length scales. We also found that inner kinetochore proteins tend to overlap the most recently duplicated subregions within centromeres. Finally, we compared chromosome X centromeres across a diverse panel of individuals and uncovered structural, epigenetic, and sequence variation at single-base resolution across these regions. In total, this work provides an unprecedented atlas of human centromeres to guide future studies of their complex and critical functions as well as their unique evolutionary dynamics. One-sentence summaryDeep characterization of fully assembled human centromeres reveals their architecture and fine-scale organization, variation, and evolution.

genomics↗

bioRxiv2020

The interaction of crossover formation and the dynamic architecture of the synaptonemal complex during meiosis

During meiosis, pairing between homologous chromosomes is stabilized by the assembly of a protein lattice known as the synaptonemal complex (SC). The SC ensures the formation of crossovers between homologous chromosomes and also regulates their distribution. However, how the SC regulates crossover formation remains elusive. We isolated an unusual mutation in C. elegans that disrupts crossover interference but not the assembly of the SC. This mutation alters the unique C-terminal domain of an essential SC protein, SYP-4, a likely ortholog of the vertebrate SC protein SIX6OS1. To characterize the structure of the SC in wild-type and mutant animals, we use three-dimensional STochastic Optical Reconstruction Microscopy (3D-STORM) to interrogate the molecular architecture of the SC in intact germline tissue from C. elegans. The approach enabled us to define positions of protein epitopes with respect to the 3D architecture of this complex. Using a probabilistic mapping approach to analyze super-resolution image data, we detect a marked structural transition in wild-type animals that coincides with crossover designation. We also found that our syp-4 mutant subtly perturbs SC architecture. Our findings add to growing evidence that the SC is an active material whose molecular organization contributes to chromosome-wide crossover regulation.

cell biology↗

bioRxiv2019

Analysis of meiosis in Pristionchus pacificus reveals plasticity in homolog pairing and synapsis within the nematode lineage

Meiosis is conserved across eukaryotes yet varies in the details of its execution. Here we describe a new comparative model system for molecular analysis of meiosis, the nematode Pristionchus pacificus, a distant relative of the widely studied model organism Caenorhabditis elegans. P. pacificus shares many anatomical and other features that facilitate analysis of meiosis in C. elegans. However, while C. elegans has lost the meiosis-specific recombinase Dmc1 and evolved a recombination-independent mechanism to synapse its chromosomes, P. pacificus expresses both DMC-1 and RAD-51. We find that SPO-11 and DMC-1 are required for stable homolog pairing, synapsis, and crossover formation, while RAD-51 is dispensable for these key meiotic processes. RAD-51 and DMC-1 localize sequentially to chromosomes during meiotic prophase and show nonoverlapping functions. We also present a new genetic map for P. pacificus that reveals a crossover landscape very similar to that of C. elegans, despite marked divergence in the regulation of synapsis and crossing-over between these lineages.

cell biology↗