Publications by authors named "J Jachowicz"

Article Synopsis
  • DNA damage repair is essential for genomic integrity and cellular health, but detecting it in individual cells has been challenging.
  • The study uses innovative techniques (DamID and ChIC sequencing) to analyze how repair proteins localize in response to DNA double-strand breaks, revealing variability in damage locations and repair features.
  • Findings indicate that repair proteins cluster in large chromatin hubs, enhancing their coordination and suggesting a preference for cooperative repair mechanisms across the genome.
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Mammalian genomes are organized into three-dimensional DNA structures called A/B compartments that are associated with transcriptional activity/inactivity. However, whether these structures are simply correlated with gene expression or are permissive/impermissible to transcription has remained largely unknown because we lack methods to measure DNA organization and transcription simultaneously. Recently, we developed RNA & DNA (RD)-SPRITE, which enables genome-wide measurements of the spatial organization of RNA and DNA.

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This protocol describes methods to design, assemble, and validate tools for targeted activation or repression of single-copy and multi-copy genes, including repetitive and transposable elements. It uses transcription activator-like effector (TALE) technology combined with VP64 activator or Kruppel-associated box (KRAB) repressor, both of which are potent transcriptional regulators that modify the epigenetic state of endogenous DNA loci. This protocol has been successfully used to simultaneously modify expression patterns of thousands of LINE-1 transposable elements and satellite repeats, both in cell culture model systems and in preimplantation mouse embryos.

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Article Synopsis
  • Xist, a long non-coding RNA, is crucial for silencing one X chromosome in females, but its precise mechanisms are unclear due to its low expression levels compared to target genes.
  • The study shows that Xist recruits the silencing protein SHARP non-stoichiometrically, enhancing its presence across the inactive X chromosome through self-assembly, which is vital for effective gene silencing.
  • Moreover, elevated Xist levels can lead to unwanted binding to autosomal regions, indicating that controlled, low expression of Xist is key for maintaining specificity and preventing spreading beyond the X chromosome.
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