A5035066706- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- Genetic Neurodegenerative Diseases
- Science, Research, and Medicine
- Biomedical and Engineering Education
- Epigenetics and DNA Methylation
- Fungal and yeast genetics research
- RNA Research and Splicing
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Ubiquitin and proteasome pathways
- Congenital heart defects research
- Histone Deacetylase Inhibitors Research
- Microtubule and mitosis dynamics
- Evolution and Genetic Dynamics
- Cardiomyopathy and Myosin Studies
- Cancer-related Molecular Pathways
- Protein Degradation and Inhibitors
- Gene Regulatory Network Analysis
- DNA and Nucleic Acid Chemistry
- Chromatin Remodeling and Cancer
- Plant Molecular Biology Research
- Genetic factors in colorectal cancer
- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
Stanford University
2015-2024
Google (United States)
2017
The University of Texas MD Anderson Cancer Center
2004-2009
Baylor College of Medicine
2001-2006
Abstract Background Somatic mutations in healthy tissues contribute to aging, neurodegeneration, and cancer initiation, yet they remain largely uncharacterized. Results To gain a better understanding of the genome-wide distribution functional impact somatic mutations, we leverage genomic information contained transcriptome uniformly call from over 7500 tissue samples, representing 36 distinct tissues. This catalog, containing 280,000 reveals wide diversity tissue-specific mutation profiles...
Metabolic signaling to chromatin often underlies how adaptive transcriptional responses are controlled. While intermediary metabolites serve as co-factors for histone-modifying enzymes during metabolic flux, these modifications contribute is poorly understood. Here, we utilize the highly synchronized yeast cycle (YMC) and find that fatty acid β-oxidation genes periodically expressed coincident with byproduct histone crotonylation. Specifically, found H3K9 crotonylation peaks when acetylation...
Abstract During development, the formation of a mature, well-functioning heart requires transformation ventricular wall from loose trabecular network into dense compact myocardium at mid-gestation. Failure to is associated in humans with congenital diseases such as left non-compaction (LVNC). The mechanisms regulating myocardial compaction are however still poorly understood. Here, we show that deletion Ino80 chromatin remodeler vascular endothelial cells prevents developing mouse heart....
The YEATS domain, found in a number of chromatin-associated proteins, has recently been shown to have the capacity bind histone lysine acetylation. Here, we show that domain Taf14, member key transcriptional and chromatin-modifying complexes yeast, is selective reader H3 Lys9 acetylation (H3K9ac). Structural analysis reveals acetylated sandwiched an aromatic cage formed by F62 W81. Disruption this binding cells impairs gene transcription DNA damage response. Our findings establish highly...
Abstract Aims Non-compaction cardiomyopathy is a devastating genetic disease caused by insufficient consolidation of ventricular wall muscle that can result in inadequate cardiac performance. Despite being the third most common cardiomyopathy, mechanisms underlying disease, including cell types involved, are poorly understood. We have previously shown endothelial cell-specific deletion chromatin remodeller gene Ino80 results defective coronary vessel development leads to non-compaction...
ATP-dependent chromatin remodeling complexes are essential for transcription regulation, and yet it is unclear how these multisubunit coordinate their activities to facilitate diverse transcriptional responses. In this study, we found that the conserved Arp5 Ies6 subunits of Saccharomyces cerevisiae INO80 chromatin-remodeler form an abundant distinct subcomplex in vivo stimulate INO80-mediated activity vitro. Moreover, our genomic studies reveal relative occupancy Arp5-Ies6 correlates with...
AbstractModulation of chromatin is essential to nuclear processes that utilize DNA, such as transcription, replication, and repair. For example, transcription assisted by histone post-translational modifications, well chromatin-remodeling complexes, which alter the structure chromatin. Furthermore, recent advancements in fields DNA repair reveal both modifications complexes are for lesions. In particular, chromatin-modifying INO80 complex Tip60 acetyltransferase complex, associate with...
ATP-dependent chromatin remodeling complexes have been implicated in the regulation of transcription, replication, and more recently DNA double-strand break repair. Here we report that Ies3p subunit Saccharomyces cerevisiae INO80 complex interacts with a conserved tetratricopeptide repeat domain telomerase protein Est1p. Deletion IES3 some other subunits induced telomere elongation altered position effect. In telomerase-negative mutants, loss delayed emergence recombinational survivors...
Adaptive survival requires the coordination of nutrient availability with expenditure cellular resources. For example, in nutrient-limited environments, 50% all S. cerevisiae genes synchronize and exhibit periodic bursts expression respiration cell division yeast metabolic cycle (YMC). Despite importance proliferative synchrony, majority YMC regulators are currently unknown. Here, we demonstrate that INO80 chromatin-remodeling complex is required to coordinate gene expression. Specifically,...
The retinoblastoma protein, pRb, controls transcription through recruitment of histone deacetylase to particular E2F-responsive genes. We determined the acetylation level individual nucleosomes present in cyclin E promoter RB +/+ and −/− mouse embryo fibroblasts. also effects pRb on nucleosomal conformation by examining thiol reactivity H3 nucleosomes. found that represses deacetylation a single nucleosome, which it 1 bind. In addition, this nucleosome is modulated pRb-directed activity....
A complex interplay between multiple chromatin modifiers is critical for cells to regulate structure and accessibility during essential DNA-templated processes such as transcription. However, the coordinated activities of these in regulation gene expression are not fully understood. We previously determined that budding yeast histone H4 methyltransferase Set5 functions together with Set1, H3K4 methyltransferase, specific cellular contexts. Here, we sought understand relationship...
Chromatin remodeling complexes are essential for gene expression programs that coordinate cell function with metabolic status. However, how these remodelers integrated in stability pathways is not well known. Here, we report an expansive genetic screen chromatin and regulators Saccharomyces cerevisiae. We found that, unlike the SWR1 remodeler, INO80 complex composed of multiple distinct functional subunit modules. identified a strikingly divergent signature Ies6 module links to homeostasis....