Biomedical subjects

Andrew Emili

Publications and source records attributed to Andrew Emili.

3 recordsLinked to original sources

PubMed2026

Cohesin preservation across mitosis contributes to restart transcription via Cdk9-mediated activation of RNAPol2.

Cohesin organizes 3D genome architecture yet its acute depletion in vitro minimally affects transcription, leaving its regulatory role puzzling. We hypothesized that cohesin function is relevant when first encounters chromatin after mitosis. Using in vivo labeling and cell-cycle synchronization in human cells, we demonstrate that cohesin complexes persist through mitosis. This inherited pool dominates over newly translated cohesin during telophase-G1, highlighting the relevance of such transmission. Acute depletion of cohesin Rad21 at mitotic exit impairs the expression of hundreds of genes, mostly downregulated, enriched on functions related to tissue growth and development. Rad21 binds the promoter of this group of genes. Remarkably, we uncover a direct interaction during the M-G1 transition between Rad21 and Cdk9, the kinase component of transcription elongation factor b (pTEFb) complex. Rad21 loss impairs Cdk9 chromatin association, reducing active-elongating RNAPol2 at down-regulated genes. Overall, preserving cohesin across mitosis enables post-mitotic transcriptional reactivation via Cdk9, establishing tissue-specific expression programs.

RNA polymerase 2↗

PubMed2026

Proteolytic activation of c-MYC facilitated by DOT1L.

c-MYC is a key regulator of growth and metabolism. Functional and molecular cooperation between the H3K79 methyltransferase DOT1L and c-MYC has been reported in several human cancer types, but the nature of their interaction remains undefined. We demonstrate that DOT1L and MYC [Myc and Mondo-like (MML-1) in Caenorhabditis elegans] coregulate genes in the nematode model and mammalian cancer cells. Moreover, both c-MYC and MML-1 exhibit cleavage products facilitated by DOT1L function. Surprisingly, we found a similarity between a conserved sequence in DOT1 proteins and the DDI-family protease catalytic motif. We characterize a c-MYC sequence preceding the DNA-binding domain as a site of nuclear proteolytic cleavage, demonstrate its importance for transcription activation by c-MYC, and propose that c-MYC is activated by a protease, as previously reported for Nuclear factor erythroid 2-related factor (NRF) and SREBP transcription factors. Our results suggest that DOT1L may activate c-MYC and other transcription factors in the nucleus by acting as a protease.

Animals↗

PubMed2024

PANAMA-enabled high-sensitivity dual nanoflow LC-MS metabolomics and proteomics analysis.

High-sensitivity nanoflow liquid chromatography (nLC) is seldom employed in untargeted metabolomics because current sample preparation techniques are inefficient at preventing nanocapillary column performance degradation. Here, we describe an nLC-based tandem mass spectrometry workflow that enables seamless joint analysis and integration of metabolomics (including lipidomics) and proteomics from the same samples without instrument duplication. This workflow is based on a robust solid-phase micro-extraction step for routine sample cleanup and bioactive molecule enrichment. Our method, termed proteomic and nanoflow metabolomic analysis (PANAMA), improves compound resolution and detection sensitivity without compromising the depth of coverage as compared with existing widely used analytical procedures. Notably, PANAMA can be applied to a broad array of specimens, including biofluids, cell lines, and tissue samples. It generates high-quality, information-rich metabolite-protein datasets while bypassing the need for specialized instrumentation.

Proteomics↗