Atg7, a critical component of autophagy machinery, is essential for counteracting hematopoietic aging. However, the non-autophagic role of Atg7 on hematopoietic cells remains fundamentally unclear. In this study, we found that loss of Atg7, but not Atg5, another autophagy-essential gene, in the hematopoietic system reduces CD11b myeloid cellularity including CD11bLy6G and CD11bLy6G populations in mouse bone marrow. Surprisingly, Atg7 deletion causes abnormally accumulated histone H3.1 to be overwhelmingly trapped in the cytoplasm in the CD11bLy6G, but not the CD11bLy6G compartment. RNA profiling revealed extensively chaotic expression of the genes required in nucleosome assembly. Functional assays further indicated upregulated aging markers in the CD11bLy6G population. Therefore, our study suggests that Atg7 is essential for maintaining proper nucleosome assembly and limiting aging in the bone marrow CD11bLy6G population.
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http://dx.doi.org/10.18632/aging.104176 | DOI Listing |
JACS Au
January 2025
Department of Cell and Molecular Biology, Uppsala University, 751 24 Uppsala, Sweden.
Disordered regions are an important functional feature of many multidomain proteins. A prime example is proteins in membraneless organelles, which contain folded domains that engage in specific interactions and disordered low-complexity (LC) domains that mediate liquid-liquid phase separation. Studying these complex architectures remains challenging due to their conformational variability.
View Article and Find Full Text PDFPLoS Comput Biol
January 2025
Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, China.
In eukaryotes, DNA achieves a highly compact structure primarily due to its winding around the histone cores. The nature wrapping of DNA around histone core form a 1.7 left-handed superhelical turns, contributing to negative supercoiling in chromatin.
View Article and Find Full Text PDFbioRxiv
January 2025
The University of Chicago, Department of Organismal Biology and Anatomy, 1027 East 57 Street, Chicago, Illinois 60637, USA.
Establishing the anterior-posterior body axis is a fundamental process during embryogenesis, and the fruit fly, , provides one of the best-known case studies of this process. In Drosophila, localized mRNA of serves as anterior determinant (AD). Bicoid engages in a concentration-dependent competition with nucleosomes and initiates symmetry-breaking along the AP axis by promoting chromatin accessibility at the loci of transcription factor (TF) genes that are expressed in the anterior of the embryo.
View Article and Find Full Text PDFGenes (Basel)
January 2025
Aix Marseille Université, Université de Toulon, CNRS, IRD, MIO UM110, 13288 Marseille, France.
This short review bridges two biological fields: ribosomes and nucleosomes-two nucleoprotein assemblies that, along with many viruses, share proteins featuring long filamentous segments at their N- or C-termini. A central hypothesis is that these extensions and tails perform analogous functions in both systems. The evolution of these structures appears closely tied to the emergence of regulatory networks and signaling pathways, facilitating increasingly complex roles for ribosomes and nucleosome alike.
View Article and Find Full Text PDFCell
January 2025
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Biochemistry, Biophysics, Chemical Biology Graduate Group, University of Pennsylvania, Philadelphia, PA, USA; Institute of Structural Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Penn Center for Genome Integrity, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:
The centromere is the chromosomal locus that recruits the kinetochore, directing faithful propagation of the genome during cell division. Using cryo-ET on human mitotic chromosomes, we reveal a distinctive architecture at the centromere: clustered 20- to 25-nm nucleosome-associated complexes within chromatin clearings that delineate them from surrounding chromatin. Centromere components CENP-C and CENP-N are each required for the integrity of the complexes, while CENP-C is also required to maintain the chromatin clearing.
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