Starting from a random RNA library expressed in yeast cells, we evolved an RNA-based transcriptional silencing domain with potency comparable to that observed when Sir1, a known silencing protein, is localized to a promoter. Using secondary-structure predictions and site-directed mutagenesis, we dissected the functional domains of the most active evolved RNA transcriptional silencer. Observed R...

The secondary structure of a pre-mRNA influences a number of processing steps including alternative splicing. Since most splicing regulatory proteins bind to single-stranded RNA, the sequestration of RNA into double strands could prevent their binding. Here, we analyzed the secondary structure context of experimentally determined splicing enhancer and silencer motifs in their natural pre-mRNA c...

Moloney murine leukemia virus (M-MLV) replication is restricted in embryonic carcinoma (EC) and embryonic stem (ES) cells, likely to protect the germ line from insertional mutagenesis. Proviral DNAs are potently silenced at the level of transcription in these cells. This silencing is largely due to an unidentified trans-acting factor that is thought to bind to the primer binding site (PBS) of M...

The chromosomes of eukaryotes are organized into structurally and functionally discrete domains that provide a mechanism to compact the DNA as well as delineate independent units of gene activity. It is believed that insulator/boundary elements separate these domains. Here we report the identification and characterization of boundary elements that flank the transcriptionally repressed HMR locus...

The mouse protocadherin (Pcdh) -α, -β, and -γ gene clusters encode more than 50 protein isoforms, the combinatorial expression of which generates vast single-cell diversity in the brain. At present, the mechanisms by which this diversity is expressed are not understood. Here we show that two transcriptional enhancer elements, HS5-1 and HS7, play a critical role in Pcdhα gene expression in mice....

A mode matching method for predicting the transmission loss of a cylindrical shaped dissipative silencer partially filled with a poroelastic foam is developed. The model takes into account the solid phase elasticity of the sound-absorbing material, the mounting conditions of the foam, and the presence of a uniform mean flow in the central airway. The novelty of the proposed approach lies in the...

The neuron-restrictive silencer factor (NRSF) represses transcription of several neuronal genes in nonneuronal cells by binding to a 21-bp element called the neuron-restrictive silencer element (NRSE). We have performed data base searches with a composite NRSE to identify additional candidate NRSF target genes. Twenty-two more genes, 17 of which are expressed mainly in neurons, were found to co...

The 15-lipoxygenase (lox) gene is expressed in a tissue-specific manner, predominantly in erythroid cells but also in airway epithelial cells and eosinophils. We demonstrate in this report that the 5' flanking DNA of the 15-lox gene contains sequences which down-regulate its activity in a variety of non-erythroid cell lines but not in two erythroid cell lines. The element has characteristics of...

Saccharomyces cerevisiae subtelomeric repeats contain silencing elements such as the core X sequence, which is present at all chromosome ends. When transplaced at HML, core X can enhance the action of a distant silencer without acting as a silencer on its own, thus fulfilling the functional definition of a protosilencer. Here we show that an ACS motif and an Abf1p-binding site participate in th...