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Disparities in American education across all levels can be traced to our nations history of racial discrimination and injustice. This inequity is rooted in a long history of discriminatory housing [...]

Abstract: Proteins that possess a chromo domain are well‐known for their roles in heterochromatin assembly and maintenance. The Heterochromatin Protein 1 (HP1) family, with a chromo domain and carboxy‐terminal chromo shadow domain, targets heterochromatin through interaction with histone H3 methylated on lysine 9 (H3K9me2/3). The structural and functional diversity of these proteins observed in both fission yeast and metazoans correlate with chromatin specialization. To expand these studies, we examined chromo domain proteins in the ciliate Tetrahymena thermophila, which has functionally diverse and developmentally regulated heterochromatin domains. We identified thirteen proteins similar to HP1. Together they possess only a fraction of the possible chromo domain subtypes and most lack a recognizable chromo shadow domain. Using fluorescence microscopy to track chromatin localization of tagged proteins through the life cycle, we show evidence that in T. thermophila this family has diversified with biological roles in RNAi‐directed DNA elimination, germline genome structure, and somatic heterochromatin. Those proteins with H3K27me3 binding sequence characteristics localize to chromatin in mature nuclei, whereas those with H3K9me2/3 binding characteristics localize to developing nuclei undergoing DNA elimination. Findings point to an expanded and diversified family of chromo domain proteins that parallels heterochromatin diversity in ciliates. [ABSTRACT FROM AUTHOR]

There is a need for improved methods to analyze transcriptional control of mammalian stem cell genes. We propose that embryonic stem cells (ESCs) will have broad utility as a model system, because they can be manipulated genetically and then differentiated into many cell types in vitro, avoiding the need to make mice. Results are presented demonstrating the utility of ESCs for analyzing cis-acting sequences using Olig2 as a model gene. Olig2 is a transcription factor that plays a key role in the development of a ventral compartment of the nervous system and the oligodendrocyte lineage. The functional role of an upstream region (USR) of the Olig2 gene was investigated in ESCs engineered at the undifferentiated stage and then differentiated into ventral neural cells with sonic hedge-hog and retinoic acid. Deletion of the USR from the native gene via gene targeting eliminates expression in ventral neural cells differentiated in cell culture. The USR is also essential for regulated expression of an Olig2 transgene inserted at a defined foreign chromosomal site. A subregion of the USR has nonspecific promoter activity in transient transfection assays in cells that do not express Olig2. Taken together, the data demonstrate that the USR contains a promoter for the Olig2 gene and suggest that repression contributes to specific expression. The technology used in this study can be applied to a wide range of genes and cell types and will facilitate research on cis-acting DNA elements of mammalian genes. [ABSTRACT FROM AUTHOR]

Objective: We investigated the ability of inhibitory neurotransmitters to alter the interleukin-1 beta (IL-1 beta)-stimulated release of interleukin-6 (IL-6) from cultured glial tumor cells., Methods: C6 rat glioblastoma cells were exposed to either IL-1 beta or its putative second messenger lysophosphatidylcholine (LPC) in the absence or presence of the inhibitory neurotransmitters somatostatin (SRIF) or gamma-aminobutyric acid (GABA). Alternatively, C6 cells were pretreated with selective inhibitors of JNK or p38 and then exposed to either IL-1 beta or LPC to determine the relative involvement of these terminal stress kinases in the stimulation of IL-6 release., Results: IL-1 beta promoted the release of IL-6 with a maximally effective concentration of 25 ng/ml. Both SRIF-14 and SRIF-28 comparably suppressed stimulated IL-6 release with an ED(50) of approximately 50 nM. GABA also prevented IL-1 beta-driven IL-6 release (ED(50) = 100 microM). IL-1 beta and LPC synergistically enhanced release of IL-6 in the presence of the beta-adrenergic receptor agonist isoproterenol (ISO); these effects were largely reversed by SRIF or GABA. The pyridinylimidazole inhibitor of p38, SB-203580, completely blocked stimulation of IL-6 release by IL-1 beta or LPC; conversely, the anthrapyrazolone JNK inhibitor, SP-600125, was ineffective in modifying stimulated IL-6 release., Conclusions: The effects of IL-1 beta and LPC on IL-6 release from glioma cells are effectively antagonized by the inhibitory neurotransmitters SRIF and GABA. On the basis of correlative studies, we propose that the ability of inhibitory transmitters such as SRIF and GABA to counter the induction of IL-6 release may entail suppression of p38 activity.