Publications by authors named "Mike V Van"

Transcriptional effectors are protein domains known to activate or repress gene expression; however, a systematic understanding of which effector domains regulate transcription across genomic, cell type and DNA-binding domain (DBD) contexts is lacking. Here we develop dCas9-mediated high-throughput recruitment (HT-recruit), a pooled screening method for quantifying effector function at endogenous target genes and test effector function for a library containing 5,092 nuclear protein Pfam domains across varied contexts. We also map context dependencies of effectors drawn from unannotated protein regions using a larger library tiling chromatin regulators and transcription factors.

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Targeting chromatin regulators to specific genomic locations for gene control is emerging as a powerful method in basic research and synthetic biology. However, many chromatin regulators are large, making them difficult to deliver and combine in mammalian cells. Here, we develop a strategy for gene control using small nanobodies that bind and recruit endogenous chromatin regulators to a gene.

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Article Synopsis
  • The study introduces a new method called HT-recruit to identify which proteins in the nucleus affect gene transcription by recruiting them to a reporter and measuring their effects through sequencing.
  • The research reveals connections between the repressor functions of specific protein domains, such as KRAB and Homeodomain, and their evolutionary age or genetic organization.
  • The findings also include new activator domains and a large resource of 600 human proteins linked to gene regulation, showcasing a scalable approach to understanding protein functions.
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  • Meiotic recombination is crucial for the segregation of homologous chromosomes, but male Caenorhabditis species face challenges due to their hemizygous X chromosome that lacks a homologous partner.* -
  • A study of several Caenorhabditis species with different reproductive strategies revealed that gonochoristic males induce more meiotic double-strand breaks (DSBs) than androdioecious males, despite similar recombination structures.* -
  • Notably, androdioecious species like C. elegans and C. briggsae show flexibility in DSB repair and transient pairing of the X chromosome, while gonochoristic species such as C. remanei and C.
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Article Synopsis
  • - In certain species, during meiosis, the heterogametic sex experiences a process called meiotic sex chromosome inactivation (MSCI), which leads to the silencing of sex chromosomes; this study focused on four Caenorhabditis species to investigate their chromatin landscape during meiosis.
  • - Although MSCI is present in all four species studied, the specific chromatin modifications associated with repression differ and do not correlate with whether the species are gonochoristic or hermaphroditic; for example, C. elegans and C. remanei have different methylation patterns compared to C. briggsae and C. brenneri.
  • - The research findings indicate that certain histone
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Article Synopsis
  • Meiosis relies on chromosome pairing and crossover recombination, with double-strand breaks (DSBs) being crucial for this process, particularly in the X chromosome of Caenorhabditis elegans males, which are hemizygous (having only one copy).
  • The study shows that DSB formation and chromosome interactions in male germ cells are closely linked, and a temporary structure called pseudosynapsis allows sister chromatids on the X chromosome to behave similarly to homologous chromosomes during repair.
  • Interestingly, X chromosome repair seems to bypass traditional homologous recombination pathways and can engage other methods like single-strand annealing, indicating a unique adaptation for the repair mechanisms in hemizygous sex chromosomes.
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