A5021375953- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Acute Myeloid Leukemia Research
- Cancer-related gene regulation
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- Genetics and Neurodevelopmental Disorders
- Cancer and biochemical research
- Acute Lymphoblastic Leukemia research
- Hormonal Regulation and Hypertension
- Estrogen and related hormone effects
- Immunodeficiency and Autoimmune Disorders
- Genomics, phytochemicals, and oxidative stress
- Hematological disorders and diagnostics
University of Colorado Boulder
2022-2025
University of Chicago
2015-2021
University of Illinois Chicago
2010-2012
University of Illinois Urbana-Champaign
2010
National Institute of Diabetes and Digestive and Kidney Diseases
2004
National Institutes of Health
2004
Epigenetic regulation underlies the robust changes in gene expression that occur during development. How precisely epigenetic enzymes contribute to development and differentiation processes is largely unclear. Here we show one of removes activating mark trimethylated lysine 4 on histone H3, (K)-specific demethylase 5A (KDM5A), reinforces effects retinoblastoma (RB) family transcriptional repressors differentiation. Global location analysis showed KDM5A cooccupies a substantial portion target...
How cyclin-dependent kinase 7 (CDK7) coordinately regulates the cell cycle and RNA polymerase II transcription remains unclear. Here, high-resolution cryo–electron microscopy revealed how two clinically relevant inhibitors block CDK7 function. In cells, inhibition rapidly suppressed transcription, but constitutively active genes were disproportionately affected versus stimulus-responsive. Distinct factors (TFs) regulate constitutive stimulus-responsive genes. Accordingly, TFs refractory to...
Histones are post-translationally modified by multiple histone-modifying enzymes, which in turn influences gene expression. Much of the work field to date has focused on genetic, biochemical and structural characterization these enzymes. The most recent genome-wide methods provide insights into specific recruitment enzymes vivo and, therefore, onto mechanisms establishing a differential expression pattern. Here we focus involved placement two contrasting histone marks, H3 lysine 4 (H3K4)...
MLL-rearranged leukemia depends on H3K79 methylation. Depletion of this transcriptionally activating mark by DOT1L deletion or high concentrations the inhibitor pinometostat downregulates HOXA9 and MEIS1 , consequently reduces survival. Yet, some leukemias are inexplicably susceptible to low-dose pinometostat, far below that downregulate canonical proliferation pathway. In context, we define alternative pathways more directly derive from H3K79me2 loss. By ICeChIP-seq, is markedly depleted at...
Cancer is characterized by aberrant patterns of expression multiple genes. These major shifts in gene are believed to be due not only genetic but also epigenetic changes. The changes communicated through chemical modifications, including histone modifications. However, it unclear whether the binding histone-modifying proteins genomic regions and placing modifications efficiently discriminates corresponding genes from rest human genome. We performed analysis demethylases (HDMs)...
Recruitment of transcriptional and epigenetic factors to their targets is a key step in regulation. Prominently featured recruitment are the protein domains that bind specific histone modifications. One such domain plant homeodomain (PHD), found several chromatin-binding proteins. The factor RBP2 has multiple PHD domains, however, they have different functions (Figure 4). In particular, C-terminal domain, oncogenic fusion human leukemia, binds trimethylated lysine 4 H3 (H3K4me3). transcript...
Abstract MLL-rearranged leukemia depends on H3K79 methylation. Depletion of this transcriptionally-activating mark by DOT1L deletion or high concentrations the inhibitor pinometostat downregulates HOXA9 and MEIS1 , consequently reduces survival. Yet some leukemias are inexplicably susceptible to low-dose pinometostat, far below that downregulate canonical proliferation pathway. In context, we define alternative pathways more directly derive from H3K79me2 loss. By ICeChIP-seq, is markedly...