Magnus David Lynch

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The role of DNA sequence in determining chromatin state is incompletely understood. We have previously demonstrated that large chromosomal segments from human cells recapitulate their native chromatin state in mouse cells, but the relative contribution of local sequences versus their genomic context remains unknown. In this study, we compare orthologous(More)
Gene expression during development and differentiation is regulated in a cell- and stage-specific manner by complex networks of intergenic and intragenic cis-regulatory elements whose numbers and representation in the genome far exceed those of structural genes. Using chromosome conformation capture, it is now possible to analyze in detail the interaction(More)
A substantial amount of organismal complexity is thought to be encoded by enhancers which specify the location, timing, and levels of gene expression. In mammals there are more enhancers than promoters which are distributed both between and within genes. Here we show that activated, intragenic enhancers frequently act as alternative tissue-specific(More)
Most mammalian continuously renewing tissues are maintained by stem cells located within stem cell niches. Each niche contains a number of stem cells that replicate asymmetrically to give differentiated cells and also undergo periodic deletion and compensatory replacement by symmetrical "self-renewal" divisions of stem cells remaining within the niche. It(More)
The overall approach to pain management encompassed in these guidelines is comprehensive. It is based on objective pain assessments, utilizes both pharmacologic and nonpharmacologic interventions, and requires continual reevaluation of the patient. The NCCN Cancer Pain Practice Guidelines Panel believes that cancer pain can be well controlled in the vast(More)
The mammary epithelium contains multipotent stem cells that give rise to all differentiated cell types present within the tissue. Mammary epithelial stem cells have been prospectively purified from dissociated mammary epithelium on the basis of cell surface antigen expression. It has become apparent in recent years that for breast cancer and other(More)
At present, the molecular mechanisms by which stem cells commit to and differentiate towards specific lineages are poorly characterized, and will need to be better understood before stem cells can be exploited fully in experimental and clinical settings. Transcriptional regulation, the ability to turn genes on and off, lies at the heart of these processes(More)
It has long been suspected that cellular senescence is an anticancer mechanism; however, it has been difficult to understand the advantage for the organism of retaining mutant cells in a postmitotic state rather than simply deleting them by apoptosis. It is proposed that in certain circumstances apoptosis promotes neoplasia by causing cells adjacent to the(More)
Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed(More)