Publications

Spt6-Spn1 interaction is required for RNA Polymerase II association and precise nucleosome positioning along transcribed genes

Abstract Spt6-Spn1 is an essential histone chaperone complex that associates with RNA Polymerase II (RNAPII) and reassembles nucleosomes during gene transcription. While the interaction between Spt6 and Spn1 is important for its histone deposition and transcription functions, a precise mechanistic understanding is still limited. Here, using temperature sensitive alleles of spt6 and spn1 that disrupt … Read more

Early life exposure to vitamin D deficiency impairs molecular mechanisms that regulate liver cholesterol biosynthesis, energy metabolism, inflammation, and detoxification

Introduction: Emerging data suggests liver disease may be initiated during development when there is high genome plasticity and the molecular pathways supporting liver function are being developed.

CHD4 and SMYD1 repress common transcriptional programs in the developing heart

Abstract Regulation of chromatin states is essential for proper temporal and spatial gene expression. Chromatin states are modulated by remodeling complexes composed of components that have enzymatic activities. CHD4 is the catalytic core of the nucleosome remodeling and deacetylase (NuRD) complex, which represses gene transcription. However, it remains to be determined how CHD4, a ubiquitous … Read more

The tardigrade Hypsibius exemplaris dramatically upregulates DNA repair pathway genes in response to ionizing radiation

Summary   Tardigrades can survive remarkable doses of ionizing radiation, up to about 1,000 times the lethal dose for humans. How they do so is incompletely understood. We found that the tardigrade Hypsibius exemplaris suffers DNA damage upon gamma irradiation, but the damage is repaired. We show that this species has a specific and robust … Read more

Von Hippel Lindau tumor suppressor controls m6A-dependent gene expression in renal tumorigenesis

Abstract N6-Methyladenosine (m6A) is the most abundant posttranscriptional modification, and its contribution to cancer evolution has recently been appreciated. Renal cancer is the most common adult genitourinary cancer, approximately 85% of which is accounted for by the clear cell renal cell carcinoma (ccRCC) subtype characterized by VHL loss. However, it is unclear whether VHL loss … Read more

Gastrulation-stage alcohol exposure induces similar rates of craniofacial malformations in male and female C57BL/6J mice

Background Prenatal alcohol exposure during gastrulation (embryonic day [E] 7 in mice, ~3rd week of human pregnancy) impairs eye, facial, and cortical development, recapitulating birth defects characteristic of Fetal Alcohol Syndrome (FAS). However, it is not known whether the prevalence or severity of craniofacial features associated with FAS is affected by biological sex. Methods The … Read more

New BARC article: Gestational diabetes mellitus placentas exhibit epimutations at placental development genes

Gestational diabetes mellitus (GDM) is a maternal metabolic disorder that perturbs placental development and increases the risk of offspring short- and long-term metabolic disorders. The mechanisms by which GDM impairs placental development remain poorly understood. Here, we defined the DNA methylome of GDM placentas and determined whether GDM perturbs methylation at genes important for placental … Read more

BARC Research Associate position open!

The UNC Integrated Genomics Cores and Bioinformatic and Analytics Research Collaborative (BARC) is looking for a Research Associate/Analyst. The analyst will provide bioinformatics and analytical support to a large cancer-focused project, and act as a consultant and analyst to projects in the UNC research community for BARC and a precision medicine initiative (https://www.med.unc.edu/ppmh/). Of top priority BARC projects are COVID-19 genomics analyses, such as … Read more

New BARC article in NEJ: Enterovirus D68 in the Anterior Horn Cells of a Child with Acute Flaccid Myelitis

To the Editor: Acute flaccid myelitis (AFM) is a poliomyelitis-like paralyzing illness in children. Since an outbreak of AFM in the United States in 2014, evidence has emerged suggesting that enterovirus D68 (EV-D68) causes AFM.1 The virus has been detected in respiratory specimens obtained from patients with AFM, but it has rarely been detected in … Read more

Multivalent DNA and nucleosome acidic patch interactions specify VRK1 mitotic localization and activity

A key role of chromatin kinases is to phosphorylate histone tails during mitosis to spatiotemporally regulate cell division. Vaccinia-related kinase 1 (VRK1) is a serine-threonine kinase that phosphorylates histone H3 threonine 3 (H3T3) along with other chromatin-based targets. While structural studies have defined how several classes of histone-modifying enzymes bind to and function on nucleosomes, … Read more