A5005184199- Ion channel regulation and function
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Nicotinic Acetylcholine Receptors Study
- Neurobiology and Insect Physiology Research
- RNA regulation and disease
- Neuroscience and Neural Engineering
- RNA and protein synthesis mechanisms
- Neuropeptides and Animal Physiology
- Pancreatic function and diabetes
- Virus-based gene therapy research
- Zebrafish Biomedical Research Applications
- Autism Spectrum Disorder Research
- RNA modifications and cancer
- Neurogenesis and neuroplasticity mechanisms
- RNA Interference and Gene Delivery
- Bacteriophages and microbial interactions
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- Animal Genetics and Reproduction
- Erythrocyte Function and Pathophysiology
- Chromatin Remodeling and Cancer
Oregon Health & Science University
2015-2024
Vollum Institute
2015-2024
Howard Hughes Medical Institute
2006-2016
State University of New York
2001-2013
Stony Brook University
1999-2013
University of Chicago
2005
Harvard University
1986-2002
University of California, San Diego
1980-2002
The Wistar Institute
2002
Institute of Neurobiology
2001
We have examined the regulation of somatostatin gene expression by cAMP in PC12 rat pheochromocytoma cells transfected with gene. Forskolin at 10 microM caused a 4-fold increase mRNA levels within 4 hr treatment stably cells. Chimeric genes containing promoter fused to bacterial reporter encoding chloramphenicol acetyltransferase were also induced To delineate sequences required for response cAMP, we constructed series deletion mutants. Our studies defined region between 60 and 29 base pairs...
Expression of the type II voltage-dependent sodium channel gene is restricted to neurons by a silencer element active in nonneuronal cells. We have cloned cDNA coding for transcription factor (REST) that binds this element. recombinant REST protein confers ability silence reporter genes neuronal cell types lacking native protein, whereas expression dominant negative form cells relieves silencing mediated protein. transcripts developing mouse embryos are detected ubiquitously outside nervous...
MicroRNAs (miRNAs) are implicated in both tissue differentiation and maintenance of identity. In most cases, however, the mechanisms underlying their regulation not known. One brain-specific miRNA, miR-124a, decreases levels hundreds nonneuronal transcripts, such that its introduction into HeLa cells promotes a neuronal-like mRNA profile. The transcriptional repressor, RE1 silencing transcription factor (REST), has reciprocal activity, inhibiting expression neuronal genes cells. Here, we...
Membrane excitability in different tissues is due, large part, to the selective expression of distinct genes encoding voltage-dependent sodium channel. Although predominant channels brain, skeletal muscle, and cardiac muscle have been identified, major channel types responsible for within peripheral nervous system remained elusive. We now describe deduced primary structure a channel, nerve type 1 (PN1), which expressed at high levels throughout targeted terminals cultured dorsal root...
Several genes encoding proteins critical to the neuronal phenotype, such as brain type II sodium channel gene, are expressed high levels only in neurons. This cell specificity is due, part, long-term repression nonneural cells mediated by repressor protein REST/NRSF (RE1 silencing transcription factor/neural-restrictive factor). We show here that CoREST, a newly identified human protein, functions corepressor for REST. A single zinc finger motif REST required CoREST interaction. Mutations of...
The molecular mechanisms by which central nervous system–specific genes are expressed only in the system and repressed other tissues remain a issue developmental regulatory biology. Here, we report that zinc-finger gene-specific repressor element RE-1 silencing transcription factor/neuronal restricted factor (REST/NRSF) can mediate extraneuronal restriction imposing either active repression via histone deacetylase recruitment or long-term gene using distinct functional complex. Silencing of...
Newborn neurons in the dentate gyrus of adult hippocampus rely upon cAMP response element binding protein (CREB) signaling for their differentiation into mature granule cells and integration network. Among its many targets, transcription factor CREB activates expression a gene locus that produces two microRNAs, miR-132 miR-212. In cultured cortical hippocampal neurons, functions downstream from to mediate activity-dependent dendritic growth spine formation variety pathways. To investigate...
Identifying the downstream targets of microRNAs (miRNAs) is essential to understanding cellular regulatory networks. We devised a direct biochemical method for miRNA target discovery that combined RNA-induced silencing complex (RISC) purification with microarray analysis bound mRNAs. Because miR-124a have been analyzed, we chose it as our model. honed approach both by examining determinants stable binding between RISC and synthetic RNAs in vitro determining dependency repression...
To characterize the precursor of mammalian thyrotropin-releasing hormone (TRH), a rat hypothalamic λgt11 library was screened with an antiserum directed against synthetic peptide representing portion TRH prohormone. The nucleotide sequence immunopositive complementary DNA encoded protein molecular weight 29,247. This contained five copies Gln-His-Pro-Gly flanked by paired basic amino acids and could therefore generate molecules. In addition, potential cleavage sites in produce other non-TRH...
Reactivation of fetal hemoglobin (HbF) in adults ameliorates the severity common β-globin disorders. The transcription factor BCL11A is a critical modulator switching and HbF silencing, yet molecular mechanism through which coordinates developmental switch incompletely understood. Particularly, identities cooperating protein complexes their roles expression erythroid development remain largely unknown. Here we determine interacting partner proteins cells by proteomic screen. found within...
De novo mutations in the X-linked gene encoding transcription factor methyl-CpG binding protein 2 (MECP2) are most frequent cause of neurological disorder Rett syndrome (RTT). Hemizygous males usually die neonatal encephalopathy. Heterozygous females survive into adulthood but exhibit severe symptoms including microcephaly, loss purposeful hand motions and speech, motor abnormalities, which appear after a period apparently normal development. Most studies have focused on male mouse models...
BRAF35, a structural DNA-binding protein, initially was identified as component of large BRCA2-containing complex. Biochemical analysis revealed the presence smaller core-BRAF35 complex devoid BRCA2. Here we report isolation six-subunit with capacity to deacetylate histones, termed BRAF-histone deacetylase (BHC), from human cells. BHC contains polypeptides reminiscent chromatin-remodeling complexes SWI/SNF and NuRD (nucleosome remodeling deacetylating). Similar NuRD, an Mi2-like subunit,...