A5053327588- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- RNA modifications and cancer
- Plant Molecular Biology Research
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- Endoplasmic Reticulum Stress and Disease
- Cancer-related molecular mechanisms research
- Fungal Infections and Studies
- COVID-19 Clinical Research Studies
- Plant and Fungal Interactions Research
- Chromosomal and Genetic Variations
- Immune cells in cancer
- Cellular transport and secretion
- Plant Reproductive Biology
- interferon and immune responses
- CRISPR and Genetic Engineering
- Lysosomal Storage Disorders Research
- Cancer-related gene regulation
- Plant Disease Resistance and Genetics
- Viral Infectious Diseases and Gene Expression in Insects
- Genomics and Phylogenetic Studies
- Receptor Mechanisms and Signaling
- Adipose Tissue and Metabolism
- Virus-based gene therapy research
Washington State University
2022-2024
University of California, San Diego
2014-2023
Salk Institute for Biological Studies
2016-2019
University of Pittsburgh
2019
University of Minnesota
2019
University of Manchester
2012-2018
Howard Hughes Medical Institute
2016
Institute of Molecular Biology
2012-2014
University of California System
2014
La Jolla Alcohol Research
2012
Patterns of transcriptional activity are encoded in our genome through regulatory elements such as promoters or enhancers that, paradoxically, contain similar assortments sequence-specific transcription factor (TF) binding sites
Abstract The structure of compound leaves provides flexibility for morphological change by variation in the shapes, sizes and arrangement leaflets. Here, we conduct a multilevel analysis shape to explore developmental plasticity evolutionary potential that are basis diversification leaf shape. We use methods geometric morphometrics study shapes individual leaflets whole 20 taxa Potentilla (sensu lato). A newly developed test based on bootstrap approach suggests uncertainty molecular...
Transcriptional regulation of gene expression is a major mechanism used by plants to confer phenotypic plasticity, and yet compared with other eukaryotes or bacteria, little known about the design principles. We generated an extensive catalog nascent steady-state transcripts in Arabidopsis thaliana seedlings using global nuclear run-on sequencing (GRO-seq), 5'GRO-seq, RNA-seq reanalyzed published maize data capture characteristics plant transcription. De novo annotation accurately mapped...
The spatial and temporal regulation of transcription initiation is pivotal for controlling gene expression. Here, we introduce capped-small RNA-seq (csRNA-seq), which uses total RNA as starting material to detect start sites (TSSs) both stable unstable RNAs at single-nucleotide resolution. csRNA-seq highly sensitive acute changes in identifies an order magnitude more regulated transcripts than does RNA-seq. Interrogating tissues from species across the eukaryotic kingdoms identified...
DNA methylation is a major epigenetic modification found across species and has profound impact on many biological processes. However, its influence chromatin accessibility higher-order genome organization remains unclear, particularly in plants. Here, we present genome-wide profiles of 18 Arabidopsis mutants that are deficient CG, CHG, or CHH methylation. We find all three sequence contexts impacts heterochromatin. Many regions maintain inaccessibility when lost only one two contexts,...
Methyl readers that repress transcription DNA methylation is a conserved epigenetic mark required for gene silencing in many different organisms. However, how the methyl able to silence genes still largely unknown. Ichino et al. discovered two Arabidopsis proteins named MBD5 and MBD6 are recruited by direct recognition of methylation. These recruit class C J-domain protein SILENZIO chromatin methylated transposons. likely acts through its interaction with heat shock chaperone proteins....
Abstract Inflammation influences cancer development, progression, and the efficacy of treatments, yet mechanisms by which immune signaling drives alterations in cell transcriptome remain unclear. Using ChIP-seq, RNA-seq, GRO-seq, here we demonstrate a global overlap binding tumor-promoting p53 mutants master proinflammatory regulator NFκB that enhancer gene activation response to chronic TNF-α signaling. We show interact directly with both factors impact other’s at diverse sets active...
The TCT core promoter element is present in most ribosomal protein (RP) genes Drosophila and humans. Here we show that TBP (TATA box-binding protein)-related factor TRF2, but not TBP, required for transcription of the TCT-dependent RP genes. In cells, transcription, TATA-dependent increases or decreases upon overexpression depletion TRF2. vitro, purified TRF2 activates TATA promoters. ChIP-seq (chromatin immunoprecipitation [ChIP] combined with deep sequencing) experiments revealed...
DNA sequence signals in the core promoter, such as initiator (Inr), direct transcription initiation by RNA polymerase II. Here we show that human Inr has consensus of BBCA +1 BW at focused promoters which initiates a single site or narrow cluster sites. The analysis 7678 start sites revealed 40% with perfect match to and 16% mismatch outside CA core. TATA-like sequences are underrepresented promoters. This is key component rules specify humans.
Abstract Mechanisms by which members of the AP-1 family transcription factors play non-redundant biological roles despite recognizing same DNA sequence remain poorly understood. To address this question, here we investigate molecular functions and genome-wide binding patterns in primary immortalized mouse macrophages. ChIP-sequencing shows overlapping distinct profiles for each factor that were remodeled following TLR4 ligation. Development a machine learning approach jointly weighs hundreds...
The emergence of Zika virus (ZIKV) as a global health threat has highlighted the unmet need for ZIKV-specific vaccines and antiviral treatments. ZIKV infects dendritic cells (DC), which have pivotal functions in activating innate adaptive responses; however, mechanisms by DC function is subverted to establish infection are unclear. Here we develop genomics profiling method that enables discrete analysis ZIKV-infected versus neighboring, uninfected primary human DCs increase sensitivity...
Nature often creates complex structures by rearranging pre-existing units. One such example is the flower head (capitulum) in daisies, where a group of flowers (florets) and phyllaries (modified bracts) are arranged to superficially mimic single flower. The capitulum key taxonomical innovation that defines daisy family (Asteraceae), largest flowering plant group. However, patterning mechanisms underlying its structure remain elusive. Here, we show auxin, hormone, provides developmental cue...
Transcription factor programs mediating the immune response to coronavirus disease 2019 (COVID-19) are not fully understood. Capturing active transcription initiation from cis-regulatory elements such as enhancers and promoters by capped small RNA sequencing (csRNA-seq), in contrast capturing steady-state transcripts conventional RNA-seq, allows unbiased identification of underlying activity regulatory pathways. Here, we profile critically ill COVID-19 patients, identifying motifs that...
The development of a complex body plan requires diversity regulatory networks. Here we consider the concept TATA-box-binding protein (TBP) family proteins as “system factors” that each supports distinct set transcriptional programs. For instance, TBP activates TATA-box-dependent core promoters, whereas TBP-related factor 2 (TRF2) TATA-less promoters are dependent on TCT or downstream promoter element (DPE) motif. These findings led us to investigate evolution TRF2. occurs in Archaea and...
Infectious pathogens like airborne viruses or fungal spores are difficult to study; they require high-containment facilities, special equipment, and expertise. As such, establishing approaches such as genome editing other means identify the factors mechanisms underlying caused diseases, and, thus, promising drug targets, is costly time-intensive.
Substance abuse and addiction represent a significant public health problem that impacts multiple dimensions of society, including healthcare, the economy, workforce. In 2021, over 100,000 drug overdose deaths were reported in US, with an alarming increase fatalities related to opioids psychostimulants. Understanding fundamental gene regulatory mechanisms underlying behaviors could facilitate more effective treatments. To explore how repeated exposure alters networks brain, we combined...
Regulating transcription allows organisms to respond their environment, both within a single generation (plasticity) and across generations (adaptation). We examined transcriptional differences in gill tissues of fishes the Poecilia mexicana species complex (family Poeciliidae), which have colonized toxic springs rich hydrogen sulfide (H 2 S) southern Mexico. There are gene expression between sulfidic non-sulfidic populations, yet regulatory mechanisms mediating this variation remain poorly...
DNMT3A encodes an enzyme that carries out de novo DNA methylation, which is essential for the acquisition of cellular identity and specialized functions during differentiation. most frequently mutated gene in age-related clonal hematopoiesis. As such, mature immune cells harboring mutations can be readily detected elderly persons. Most associated with hematopoiesis are heterozygous predicted to cause loss function, indicating haploinsufficiency predominant pathogenic mechanism. Yet, impact...
Protein aggregates are a common feature of diseased and aged cells. Membrane proteins comprise quarter the proteome, yet, it is not well understood how aggregation membrane regulated what effects these can have on cellular health. We determined in yeast that derlin Dfm1 has chaperone-like activity influences misfolded protein aggregation. establish this function does require recruitment ATPase Cdc48 distinct from Dfm1’s previously identified dislocating endoplasmic reticulum (ER) to cytosol...
Unstable transcripts have emerged as markers of active enhancers in vertebrates and shown to be involved many cellular processes medical disorders. However, their prevalence role plants is largely unexplored. Here, we comprehensively captured all actively initiating (nascent) across diverse crops other using capped small (cs)RNA sequencing. We discovered that unstable are rare plants, unlike vertebrates, when present, often originate from promoters. In addition, 'distal' elements initiate...