Biology subjects

Albritton, S. E.

Publications and source records attributed to Albritton, S. E..

4 recordsLinked to original sources

bioRxiv2022

Increased gene dosage and mRNA expression from chromosomal duplications in C. elegans

Isolation of copy number variations and chromosomal duplications at high frequency in the laboratory suggested that Caenorhabditis elegans tolerates increased gene dosage. Here we addressed if a general dosage compensation mechanism acts at the level of mRNA expression in C. elegans. We characterized gene dosage and mRNA expression in three chromosomal duplications and a fosmid integration strain using DNA-seq and mRNA-seq. Our results show that on average, increased gene dosage leads to increased mRNA expression, pointing to a lack of genome-wide dosage compensation. Different genes within the same chromosomal duplication show variable levels of mRNA increase, suggesting feedback regulation of individual genes. Somatic dosage compensation and germline repression reduce the level of mRNA increase from X chromosomal duplications. Together, our results show a lack of genome-wide dosage compensation mechanism acting at the mRNA level in C. elegans and highlight the role of epigenetic and individual gene regulation contributing to the varied consequences of increased gene dosage.

genomics↗

bioRxiv2021

A noncatalytic activity of the H4K20 demethylase DPY-21 regulates condensin DC binding

Condensin is a multi-subunit SMC complex that binds to and compacts chromosomes. Here we addressed the regulation of condensin binding dynamics using C. elegans condensin DC, which represses X chromosomes in hermaphrodites for dosage compensation. We established fluorescence recovery after photobleaching (FRAP) using the SMC4 homolog DPY-27 and showed that a well-characterized ATPase mutation abolishes its binding. Next, we performed FRAP in the background of several chromatin modifier mutants that cause varying degrees of X-chromosome derepression. The greatest effect was in a null mutant of the H4K20me2 demethylase DPY-21, where the mobile fraction of condensin DC reduced from [~]30% to 10%. In contrast, a catalytic mutant of dpy-21 did not regulate condensin DC mobility. Hi-C data in the dpy-21 null mutant showed little change compared to wild type, uncoupling Hi-C measured long-range DNA contacts from transcriptional repression of the X chromosomes. Together, our results indicate that DPY-21 has a non-catalytic role in regulating the dynamics of condensin DC binding, which is important for transcription repression.

cell biology↗

bioRxiv2021

Condensin DC spreads linearly and bidirectionally from recruitment sites to create loop-anchored TADs in C. elegans

Condensins are molecular motors that compact DNA via linear translocation. In C. elegans, the X-chromosome harbors a specialized condensin that participates in dosage compensation (DC). Condensin DC is recruited to and spreads from a small number of recruit elements on the X-chromosome (rex) and is required for the formation of topologically associating domains (TADs). We take advantage of autosomes that are largely devoid of condensin DC and TADs to address how rex sites and condensin DC give rise to the formation of TADs. When an autosome and X-chromosome are physically fused, despite the spreading of condensin DC into the autosome, no TAD was created. Insertion of a strong rex on the X-chromosome results in the TAD boundary formation regardless of sequence orientation. When the same rex is inserted on an autosome, despite condensin DC recruitment, there was no spreading or features of a TAD. On the other hand, when a "super rex" composed of six rex sites or three separate rex sites are inserted on an autosome, recruitment and spreading of condensin DC led to formation of TADs. Therefore, recruitment to and spreading from rex sites are necessary and sufficient for recapitulating loop-anchored TADs observed on the X-chromosome. Together our data suggest a model in which rex sites are both loading sites and bidirectional barriers for condensin DC, a one-sided loop-extruder with movable inactive anchor.

genomics↗

bioRxiv2019

An X-specific condensin binds to gene regulatory elements and reduces histone modifications associated with active transcription in C. elegans

Condensins are evolutionarily conserved protein complexes that are required for chromosome segregation during cell division and genome organization during interphase. In C. elegans, a specialized condensin, which forms the core of the dosage compensation complex (DCC) binds to and represses X chromosome transcription. Here, we analyzed DCC localization and effect of DCC depletion and binding on histone modifications, transcription factor binding, and gene expression using ChIP-seq and mRNA-seq. Across the X, DCC binding coincides with gene regulatory sites at active chromatin and not heterochromatin. DCC is required for reducing the levels of active histone modifications, including H3K4me3 and H3K27ac, but not repressive modification H3K9me3 on the X. In X-to-autosome fusion chromosomes, DCC spreading into the autosomal sequences locally reduces the level of H3K4me3 and gene expression. Together, our results suggest that DCC fine-tunes X chromosomal transcription by binding to and modulating the activity of gene regulatory elements through reducing activating histone modifications.

genomics↗