Publications
Explore some of the Lund lab's latest projects and publications here.
Optimized and Robust Workflow for Quantifying the Canonical Histone Ubiquitination Marks H2AK119ub and H2BK120ub by LC-MS/MS
Mass spectrometry (MS) has become a powerful technique in unraveling the histone code, which is an epigenetic mechanism that regulates our genes through the deposition and removal of small chemical groups to the histone proteins that package our DNA within the cell nucleus. Although robust MS methods are available to analyze modifications on the histone N-terminal tails, routine methods for characterizing ubiquitin marks on histone C-terminal regions, especially H2AK119ub, are less robust. Here, we report the development of a simple workflow for the detection and improved quantification of the canonical histone ubiquitination marks H2AK119ub and H2BK120ub.
FGF-2 induces a failure of cell cycle progression in cells harboring amplified K-Ras, revealing new insights into oncogene-induced senescence
Paradoxically, oncogenes that drive cell cycle progression may also trigger pathways leading to senescence, thereby inhibiting the growth of tumorigenic cells. Knowledge of how these pathways operate, and how tumor cells may evade these pathways, is important for understanding tumorigenesis. The Y1 cell line, which harbors an amplification of the proto-oncogene Ras, rapidly senesces in response to the mitogen fibroblast growth factor-2 (FGF-2). To gain a more complete picture of how FGF-2 promotes senescence, we employed a multi-omics approach to analyze histone modifications, mRNA and protein expression, and protein phosphorylation in Y1 cells treated with FGF-2.
Stable isotope tracing in vivo reveals a metabolic bridge linking the microbiota to host histone acetylation
The gut microbiota influences acetylation on host histones by fermenting dietary fiber into butyrate, a short-chain fatty acid. Although butyrate could promote histone acetylation by inhibiting histone deacetylases, it may also undergo oxidation to acetyl-coenzyme A (CoA), a necessary cofactor for histone acetyltransferases. Here, we find that epithelial cells from germ-free mice harbor a loss of histone H4 acetylation across the genome except at promoter regions. Using stable isotope tracing in vivo with 13C-labeled fiber, we demonstrate that the microbiota supplies carbon for histone acetylation and that intestinal inflammation disrupts this metabolic connection.