A5033430541- Epigenetics and DNA Methylation
- Connective tissue disorders research
- Fibroblast Growth Factor Research
- Genomics and Chromatin Dynamics
- Muscle Physiology and Disorders
- RNA modifications and cancer
- Telomeres, Telomerase, and Senescence
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Adipose Tissue and Metabolism
- Muscle metabolism and nutrition
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
- Fungal and yeast genetics research
- Pluripotent Stem Cells Research
- Genetic Syndromes and Imprinting
- Genetics, Aging, and Longevity in Model Organisms
- Periodontal Regeneration and Treatments
- Receptor Mechanisms and Signaling
- bioluminescence and chemiluminescence research
- Microtubule and mitosis dynamics
- Liver physiology and pathology
- Exercise and Physiological Responses
- Nutrition and Health in Aging
- Carcinogens and Genotoxicity Assessment
University of Southern California
2010-2021
Centrum Badań Molekularnych i Makromolekularnych Polskiej Akademii Nauk
2017
Princeton University
2006-2011
Cancer Research UK
2004
University of Colorado Health
2004
Tufts University
1999
Jean Mayer Human Nutrition Research Center on Aging
1999
Highlights•Rapid PR-Set7 recruitment to DSBs is dependent on Ku70 and required for NHEJ repair•De novo H4K20 methylations at require monomethyltransferase activity•PR-Set7-mediated H4K20me1 necessary but insufficient 53BP1 nucleation•H4K20me1 facilitates Suv4-20-mediated H4K20me2 binding DSBsSummaryAlthough selective of dimethylated histone H4 lysine 20 (H4K20me2) DNA double-strand breaks (DSBs) a pivotal determinant nonhomologous end joining (NHEJ)-directed repair, the enzymes that generate...
Epitope tagging permits the detection of proteins when protein-specific antibodies are not available. However, epitope tag can reduce function tagged protein. Here we describe a cassette that be used to introduce an eight amino acid flexible linker between multiple Myc epitopes and open reading frame given gene. We show inserting improves in vivo ability telomerase subunits Est2p Est1p maintain telomere length. The methods here generally applicable improve both Saccharomyces cerevisiae...
Telomerase is a telomere dedicated reverse transcriptase that replicates the very ends of eukaryotic chromosomes. Saccharomyces cerevisiae telomerase consists TLC1 (the RNA template), Est2 catalytic subunit), and two accessory proteins, Est1 Est3, are essential in vivo for activity but dispensable catalysis vitro. functions both recruitment activation telomerase. The association Est3 with telomeres occurred largely late S/G2 phase, time when acts binding occurs. was Est1-dependent. This...
ABSTRACT Tendon and bone are attached by a transitional connective tissue that is morphologically graded from tendinous to osseous develops bipotent progenitors co-express scleraxis (Scx) Sox9 (Scx+/Sox9+). Scx+/Sox9+ have the potential differentiate into either tenocytes or chondrocytes, yet developmental mechanism spatially resolves their bipotency at tendon-bone interface during embryogenesis remains unknown. Here, we demonstrate development of within mammalian lower jaw requires FGF...
Fibroblast growth factor receptor 2 (FGFR2) promotes osteoprogenitor proliferation and differentiation during bone development, yet how the elicits these distinct cellular responses remains unclear. Analysis of FGFR2-skeletal disorder bent dysplasia syndrome (BBDS) demonstrates that FGFR2, in addition to its canonical signaling activities at plasma membrane, regulates formation from within nucleolus. Previously, we showed unique FGFR2 mutations cause BBDS reduce levels membrane diminish...
Telomeres share the ability to silence nearby transcription with heterochromatin, but requirement of heterochromatin proteins for most telomere functions is unknown. The fission yeast Rik1 protein required formation at centromeres and mating-type locus, as it recruits Clr4 histone methyltransferase, whose modification H3 triggers binding by Swi6, a conserved involved in spreading heterochromatin. Here, we demonstrate that Clr4, not are along Taz1 crucial chromosome movements during meiosis....
Abstract PR-Set7/Set8/KMT5a is the sole histone H4 lysine 20 monomethyltransferase (H4K20me1) in metazoans and essential for proper cell division genomic stability. We unexpectedly discovered that normal cellular levels of monomethylated H3 9 (H3K9me1) were also dependent on PR-Set7, but independent its catalytic activity. This observation suggested PR-Set7 interacts with an H3K9 to establish previously reported H4K20me1-H3K9me1 trans-tail ‘histone code’. Here we show specifically directly...
The proliferative potential of the liver has been well documented to decline with age. However, molecular mechanism this phenomenon is not understood. Cellular proliferation result growth factor-receptor binding and activation cellular signaling pathways regulate specific gene transcription. To determine age-related difference in proliferation, we evaluated extracellular signal-regulated kinase-mitogen-activated protein kinase events upstream pathway epidermal factor (EGF)-stimulated...
Fibroblast Growth Factor (FGF) signaling promotes self-renewal in progenitor cells by encouraging proliferation and inhibiting cellular senescence. Yet, these beneficial effects can be hijacked disease-causing mutations FGF receptor (FGFR) during embryogenesis. By studying dominant FGFR2 that are germline bent bone dysplasia syndrome (BBDS), we reveal a mechanistic connection between FGFR2, ribosome biogenesis, stress links cell fate determination to disease pathology. We previously showed...
PGC-1α4, a novel isoform of the transcriptional coactivator PGC-1α, was recently postulated to modulate expression anabolic and catabolic genes therefore regulate skeletal muscle hypertrophy. Resting levels PGC-1α4 messenger RNA (mRNA) were found increase in healthy adults after resistance training. However, acute effect exercise (RE) on populations prone progressive loss, such as postmenopausal women, has not been evaluated. Here, we investigated alterations mRNA PGC-1α1, regulator...
Purpose: Prostate cancer survivors (PCS) receive androgen deprivation therapy (ADT) as treatment for recurrent cancer, yet ADT is associated with loss of skeletal muscle and physical function. Resistance training can counter both function loss; however, an understanding the molecular responses to resistance during still undefined. This sub-analysis original randomized, controlled pilot trial investigated effects 12 weeks periodized on mRNA expression anabolic genes IGF-1, myogenin, PGC-1α4...
Fibroblast Growth Factor Receptor 2 (FGFR2) promotes osteoprogenitor cell proliferation and differentiation during bone development, yet it remains unclear how the receptor couples these distinct cellular processes. Analysis of new FGFR2‐skeletal disorder Bent Bone Dysplasia Syndrome (BBDS) suggests that receptor, in addition to its canonical activities, regulates formation within nucleolus. We previously showed FGFR2 mutations BBDS reduce levels at plasma membrane markedly diminish...
Numerous skeletal birth defects arise from mutations in genes that regulate when and where osteoprogenitor cells transition a proliferative state to one of terminal differentiation during development. Fibroblast Growth Factor Receptor 2 (FGFR2), whose cause 10 distinct disorders, is such regulator. While FGFR2 promotes both proliferation cells, how the receptor executes links these opposed activities remains unclear. Our analysis Bent Bone Dysplasia Syndrome (BBDS), FGFR2‐disorder with...
Abstract While selective binding of the tandem tudor domains p53 protein 1 (53BP1) to dimethylated histone H4 lysine 20 (H4K20me2) at DNA double strand breaks (DSBs) is well-documented be an essential event for proficient DSB repair, enzyme(s) responsible H4K20 methylation DSBs remained unknown. Contrary previous reports implicating MMSET/NSD2 methyltransferase in this pathway, we demonstrate that MMSET dispensable methylation, 53BP1 accumulation and repair. Alternatively, discovered PR-Set7...
PGC‐1α4, an isoform of the transcriptional coactivator PGC‐1α, has been postulated to regulate skeletal muscle hypertrophy through modulation anabolic and catabolic gene expression. While resting levels PGC‐1α4 mRNA expression were found increase in healthy adults after a resistance training program, acute effect exercise (RE) on population prone progressive loss, such as postmenopausal women, not investigated. We sought determine whether high‐intensity eccentric RE altered PGC‐1α isoforms...
Post‐translational modifications (PTMs) of nucleosomes are critical for genome architecture and function. Remarkably, more than 70 different sites histone PTMs have been reported; however, the identification PTM binding proteins (PTMBPs) mechanistic understanding how various translate in to biological outputs is less understood. We developed mammalian tethered catalysis (MTeC) as an vivo approach identify novel PTMBPs. To validate this approach, we first used MTeC H3K9 PTMBPs unbiased...