Jef Boeke

Jan 19, 2025 | nature.com | Yu Zhao |Julie Calame |Briardo Llorente |Carmen Hawthorne |Samuel Clay |Yizhi Cai | +6 more

AbstractThe Sc2.0 global consortium to design and construct a synthetic genome based on the Saccharomyces cerevisiae genome commenced in 2006, comprising 16 synthetic chromosomes and a new-to-nature tRNA neochromosome. In this paper we describe assembly and debugging of the 902,994-bp synthetic Saccharomyces cerevisiae chromosome synXVI of the Sc2.0 project.

May 17, 2024 | nature.com | Brian D. Piening |Maedeh Mohebnasab |Bo Xia |Jeffrey S. Stern |Weimin Zhang |Jacqueline I. Kim | +20 more

AbstractIn a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling.

May 16, 2024 | cell.com | Raquel Ordoñez |Weimin Zhang |Gwen Ellis |Yinan Zhu |André M. Ribeiro-dos-Santos |Ran Brosh | +5 more

Genomic context critically modulates regulatory function but is difficult to manipulate systematically. The murine insulin-like growth factor 2 (Igf2)/H19 locus is a paradigmatic model of enhancer selectivity, whereby CTCF occupancy at an imprinting control region directs downstream enhancers to activate either H19 or Igf2. We used synthetic regulatory genomics to repeatedly replace the native locus with 157-kb payloads, and we systematically dissected its architecture.

Feb 28, 2024 | nature.com | Bo Xia |Weimin Zhang |Xinru Zhang |Ran Brosh |Aleksandra Wudzinska |Yu Zhao | +2 more

AbstractThe loss of the tail is among the most notable anatomical changes to have occurred along the evolutionary lineage leading to humans and to the ‘anthropomorphous apes’1,2,3, with a proposed role in contributing to human bipedalism4,5,6. Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. Here we present evidence that an individual insertion of an Alu element in the genome of the hominoid ancestor may have contributed to tail-loss evolution.

Aug 28, 2023 | biorxiv.org | Jacob L. Steenwyk |Jef Boeke

AbstractAcross eukaryotic species, core histone genes display a remarkable diversity of cis-regulatory mechanisms despite their protein sequence conservation. However, the dynamics and significance of this regulatory turnover are not well understood. Here we describe the evolutionary history of core histone gene regulation across 400 million years in Saccharomycotina yeasts. We reveal diverse lineage-specific solutions to core histone expression.