Regulatory Sequences, Nucleic Acid

Publication Title: 
Molecular and Cellular Biology

The macronuclear rRNA genes (rDNA) in the ciliate Tetrahymena thermophila are normally palindromic linear replicons, containing two copies of the replication origin region in inverted orientation. A circular plasmid containing a single Tetrahymena rRNA gene (one half palindrome) joined to a tandem repeat of a 1.9-kilobase (kb) rDNA segment encompassing the rDNA replication origin and known replication control elements was used to transform Tetrahymena macronuclei by microinjection.

Yu, G. L.
Blackburn, E. H.
Publication Title: 
BMC genomics

BACKGROUND: Alzheimer's disease (AD) is intimately tied to amyloid-? (A?) peptide. Extraneuronal brain plaques consisting primarily of A? aggregates are a hallmark of AD. Intraneuronal A? subunits are strongly implicated in disease progression. Protein sequence mutations of the A? precursor protein (APP) account for a small proportion of AD cases, suggesting that regulation of the associated gene (APP) may play a more important role in AD etiology.

Lahiri, Debomoy K.
Maloney, Bryan
Rogers, Jack T.
Ge, Yuan-Wen
Publication Title: 
Trends in genetics: TIG

Transcriptional mechanisms mediated by the binding of transcription factors (TFs) to cis-acting regulatory elements (CREs) in DNA play crucial roles in directing gene expression. While TFs have been extensively studied, less effort has gone towards the identification and functional characterization of CREs and associated epigenetic modulation. However, owing to methodological and analytical advances, more comprehensive studies of regulatory elements and mechanisms are now possible.

Shibata, Mikihito
Gulden, Forrest O.
Sestan, Nenad
Publication Title: 
Genome Research

Epigenetic processes play a key role in orchestrating transcriptional regulation during development. The importance of DNA methylation in fetal brain development is highlighted by the dynamic expression of de novo DNA methyltransferases during the perinatal period and neurodevelopmental deficits associated with mutations in the methyl-CpG binding protein 2 (MECP2) gene. However, our knowledge about the temporal changes to the epigenome during fetal brain development has, to date, been limited. We quantified genome-wide patterns of DNA methylation at ?

Spiers, Helen
Hannon, Eilis
Schalkwyk, Leonard C.
Smith, Rebecca
Wong, Chloe C. Y.
O'Donovan, Michael C.
Bray, Nicholas J.
Mill, Jonathan
Publication Title: 
PLoS genetics

Large genome-wide association studies (GWAS) have identified many genetic loci associated with risk for myocardial infarction (MI) and coronary artery disease (CAD). Concurrently, efforts such as the National Institutes of Health (NIH) Roadmap Epigenomics Project and the Encyclopedia of DNA Elements (ENCODE) Consortium have provided unprecedented data on functional elements of the human genome. In the present study, we systematically investigate the biological link between genetic variants associated with this complex disease and their impacts on gene function.

Won, Hong-Hee
Natarajan, Pradeep
Dobbyn, Amanda
Jordan, Daniel M.
Roussos, Panos
Lage, Kasper
Raychaudhuri, Soumya
Stahl, Eli
Do, Ron
Publication Title: 
Genes, Brain, and Behavior

Current evidence emerging from genome-wide association studies indicates that the genetic underpinnings of complex traits are likely attributable to genetic variation that changes gene expression, rather than (or in combination with) variation that changes protein-coding sequences. This is particularly compelling with respect to psychiatric disorders, as genetic changes in regulatory regions may result in differential transcriptional responses to developmental cues and environmental/psychosocial stressors.

Barr, C. L.
Misener, V. L.
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

UDP glucuronosyltransferase (UGT) 1A6 is a major isoform in human liver that glucuronidates numerous drugs, toxins, and endogenous substrates with high interindividual variability. The molecular basis for this variability remains unknown, although it likely involves genetic and environmental factors. Phenotype-genotype studies were conducted using a well characterized human liver bank (n = 54) and serotonin glucuronidation as a UGT1A6-specific phenotype marker.

Krishnaswamy, Soundararajan
Hao, Qin
Al-Rohaimi, Abdul
Hesse, Leah M.
von Moltke, Lisa L.
Greenblatt, David J.
Court, Michael H.
Publication Title: 

The inducible IkappaB kinase (IKKi/IKKepsilon) is a recently described serine-threonine kinase that activates the transcription factors NFkappaB, interferon regulatory factor-3 (IRF3) and CCAAA/enhancer-binding protein (C/EBPdelta). Several inflammatory agents have been shown to induce the expression of the IKKi gene in macrophages and other cell types but the mechanism is unknown.

Wang, Naizhen
Ahmed, Salahuddin
Haqqi, Tariq M.
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