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Articles by R Sen
Total Records ( 3 ) for R Sen
  R Sen and R. Grosschedl

Transcriptional enhancers are key determinants of developmentally regulated gene expression. Models of enhancer function must distinguish between analog or digital control of transcription, as well as their requirement to initiate or maintain transcriptional activity of a gene. In light of a recent study by Chong and colleagues (pp. 659–669) providing evidence of a transient requirement of an enhancer associated with the CD4 gene, we discuss possible mechanisms by which transcriptional memory can be propagated in the absence of enhancers.

  Z Guan , C. M Hughes , S Kosiyatrakul , P Norio , R Sen , S Fiering , C. D Allis , E. E Bouhassira and C. L. Schildkraut

Experimental attempts to activate replication origins within the temporal transition region in the IgH locus in mouse embryonic stem cells were not successful, and thus, why and how they become activated in B cells remains unclear.

  D Rajagopal , R. W Maul , A Ghosh , T Chakraborty , A. A Khamlichi , R Sen and P. J. Gearhart

Repetitive DNA sequences in the immunoglobulin switch µ region form RNA-containing secondary structures and undergo hypermutation by activation-induced deaminase (AID). To examine how DNA structure affects transcription and hypermutation, we mapped the position of RNA polymerase II molecules and mutations across a 5-kb region spanning the intronic enhancer to the constant µ gene. For RNA polymerase II, the distribution was determined by nuclear run-on and chromatin immunoprecipitation assays in B cells from uracil-DNA glycosylase (UNG)–deficient mice stimulated ex vivo. RNA polymerases were found at a high density in DNA flanking both sides of a 1-kb repetitive sequence that forms the core of the switch region. The pileup of polymerases was similar in unstimulated and stimulated cells from Ung–/– and Aid–/–Ung–/– mice but was absent in cells from mice with a deletion of the switch region. For mutations, DNA was sequenced from Ung–/– B cells stimulated in vivo. Surprisingly, mutations of A nucleotides, which are incorporated by DNA polymerase , decreased 10-fold before the repetitive sequence, suggesting that the polymerase was less active in this region. We propose that altered DNA structure in the switch region pauses RNA polymerase II and limits access of DNA polymerase during hypermutation.

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