In mammals, HP1-mediated heterochromatin forms positionally and mechanically stable genomic domains even though the component HP1 paralogs, HP1α, HP1β, and HP1γ, display rapid on-off dynamics. Here, we investigate whether phase-separation by HP1 proteins can explain these biological observations. Using bulk and single-molecule methods, we show that, within phase-separated HP1α-DNA condensates, HP1α acts as a dynamic liquid, while compacted DNA molecules are constrained in local territories. These condensates are resistant to large forces yet can be readily dissolved by HP1β. Finally, we find that differences in each HP1 paralog's DNA compaction and phase-separation properties arise from their respective disordered regions. Our findings suggest a generalizable model for genome organization in which a pool of weakly bound proteins collectively capitalize on the polymer properties of DNA to produce self-organizing domains that are simultaneously resistant to large forces at the mesoscale and susceptible to competition at the molecular scale.
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http://dx.doi.org/10.7554/eLife.64563 | DOI Listing |
The recruitment of Heterochromatin Protein 1 (HP1) partners is essential for heterochromatin assembly and function, yet our knowledge regarding their organization in heterochromatin remains limited. Here we show that interactors engage the Drosophila HP1 (HP1a) dimer through a degenerate and expanded form of the previously identified PxVxL motif, which we now term HP1a Access Codes (HACs). These HACs reside in disordered regions, possess high conservation among Drosophila homologs, and contain alternating hydrophobic residues nested in a cluster of positively charged amino acids.
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December 2024
Laboratory of Chromosome Engineering, Department of Frontier Research and Development, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu 292-0818, Japan.
Aneuploidy is caused by chromosomal missegregation and is frequently observed in cancers and hematological diseases. Therefore, it is important to understand the molecular mechanisms underlying chromosomal segregation. The centromere's intricate structure is crucial for proper chromosome segregation, with heterochromatin at the pericentromeric α-satellites playing a key role.
View Article and Find Full Text PDFFish Shellfish Immunol
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Department of Animal Production, Faculty of Agriculture, Zagazig University, Zagazig, Egypt.
In shrimp aquaculture, enhancing health and disease resistance is crucial for sustainable production. This study investigates the pioneering effects of astaxanthin-enriched microalgal powder from Haematococcus pluvialis (HP) on Pacific white shrimp (Litopenaeus vannamei), focusing on growth efficiency, body composition, immune and antioxidant responses, intestinal health, histopathology, gene expression, and resistance against Fusarium solani. Shrimp (initial weight 5.
View Article and Find Full Text PDFNat Commun
November 2024
Institute for Pharmaceutical Chemistry, Department of Biochemistry, Chemistry and Pharmacy, Goethe University Frankfurt, Max-von-Laue-Straße 9, 60438, Frankfurt, Germany.
Recent successes in developing small molecule degraders that act through the ubiquitin system have spurred efforts to extend this technology to other mechanisms, including the autophagosomal-lysosomal pathway. Therefore, reports of autophagosome tethering compounds (ATTECs) have received considerable attention from the drug development community. ATTECs are based on the recruitment of targets to LC3/GABARAP, a family of ubiquitin-like proteins that presumably bind to the autophagosome membrane and tether cargo-loaded autophagy receptors into the autophagosome.
View Article and Find Full Text PDFNucleic Acids Res
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Institute of Microbial Technology, Sector 39A, Chandigarh 160036, India.
Prions represent epigenetic regulator proteins that can self-propagate their structure and confer their misfolded structure and function on normally folded proteins. Like the mammalian prion PrPSc, prions also occur in fungi. While a few prions, like Swi1, affect gene expression, none are shown to affect heterochromatin structure and function.
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