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Conserved chromosomal HP1 proteins capable of binding to histone H3 methylated at lysine 9 are believed to provide a dynamic platform for the recruitment and/or spreading of various regulatory proteins involved in diverse chromosomal processes. The fission yeast Schizosaccharomyces pombe HP1 family members Chp2 and Swi6 are important for heterochromatin assembly and transcriptional silencing, but their precise roles are not fully understood. Here, we show that Swi6 and Chp2 associate with histone deacetylase (HDAC) protein complexes containing class I HDAC Clr6 and class II HDAC Clr3 (a component of Snf2/HDAC repressor complex), which are critical for transcriptional silencing of centromeric repeats targeted by the heterochromatin machinery. Mapping of RNA polymerase (Pol) II distribution in single and double mutant backgrounds revealed that Swi6 and Chp2 proteins and their associated HDAC complexes have overlapping functions in limiting Pol II occupancy across pericentromeric heterochromatin domains. The purified Swi6 fraction also contains factors involved in various chromosomal processes such as chromatin remodeling and DNA replication. Also, Swi6 copurifies with Mis4 protein, a cohesin loading factor essential for sister chromatid cohesion, and with centromere-specific histone H3 variant CENP-A, which is incorporated into chromatin in a heterochromatin-dependent manner. These analyses suggest that among other functions, HP1 proteins associate with chromatin-modifying factors that in turn cooperate to assemble repressive chromatin; thus, precluding accessibility of underlying DNA sequences to transcriptional machinery.
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http://dx.doi.org/10.1073/pnas.0813063106 | 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.
View Article and Find Full Text PDFNucleic Acids Res
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
January 2025
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
December 2024
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.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!