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1.
Cell ; 184(25): 6174-6192.e32, 2021 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-34813726

RESUMEN

The lncRNA Xist forms ∼50 diffraction-limited foci to transcriptionally silence one X chromosome. How this small number of RNA foci and interacting proteins regulate a much larger number of X-linked genes is unknown. We show that Xist foci are locally confined, contain ∼2 RNA molecules, and nucleate supramolecular complexes (SMACs) that include many copies of the critical silencing protein SPEN. Aggregation and exchange of SMAC proteins generate local protein gradients that regulate broad, proximal chromatin regions. Partitioning of numerous SPEN molecules into SMACs is mediated by their intrinsically disordered regions and essential for transcriptional repression. Polycomb deposition via SMACs induces chromatin compaction and the increase in SMACs density around genes, which propagates silencing across the X chromosome. Our findings introduce a mechanism for functional nuclear compartmentalization whereby crowding of transcriptional and architectural regulators enables the silencing of many target genes by few RNA molecules.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Mitocondriales/metabolismo , ARN Largo no Codificante/metabolismo , Cromosoma X/metabolismo , Animales , Línea Celular , Células Madre Embrionarias , Fibroblastos , Silenciador del Gen , Humanos , Ratones , Unión Proteica , Inactivación del Cromosoma X
2.
Nat Methods ; 2024 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-39420143

RESUMEN

Light sheet microscopy is a powerful technique for high-speed three-dimensional imaging of subcellular dynamics and large biological specimens. However, it often generates datasets ranging from hundreds of gigabytes to petabytes in size for a single experiment. Conventional computational tools process such images far slower than the time to acquire them and often fail outright due to memory limitations. To address these challenges, we present PetaKit5D, a scalable software solution for efficient petabyte-scale light sheet image processing. This software incorporates a suite of commonly used processing tools that are optimized for memory and performance. Notable advancements include rapid image readers and writers, fast and memory-efficient geometric transformations, high-performance Richardson-Lucy deconvolution and scalable Zarr-based stitching. These features outperform state-of-the-art methods by over one order of magnitude, enabling the processing of petabyte-scale image data at the full teravoxel rates of modern imaging cameras. The software opens new avenues for biological discoveries through large-scale imaging experiments.

3.
Nat Cell Biol ; 24(9): 1332-1340, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36008480

RESUMEN

Since the discovery of transposons, their sheer abundance in host genomes has puzzled many. While historically viewed as largely harmless 'parasitic' DNAs during evolution, transposons are not a mere record of ancient genome invasion. Instead, nearly every element of transposon biology has been integrated into host biology. Here we review how host genome sequences introduced by transposon activities provide raw material for genome innovation and document the distinct evolutionary path of each species.


Asunto(s)
Elementos Transponibles de ADN , Domesticación , Animales , Elementos Transponibles de ADN/genética , Evolución Molecular , Mamíferos
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