Sequences affecting the V(D)J recombinational activity of the IgH intronic enhancer in a transgenic substrate.

Content Provider	Semantic Scholar
Author	Fernex, Corinne Caillol, Danielle H. Capone, Myriam Krippl, Bernd Ferrier, Pierre
Copyright Year	1994
Abstract	The immunoglobulin heavy chain intronic transcriptional enhancer (E mu) is part of a complex cis-regulatory DNA region which has notably been shown to modulate V(D)J rearrangements of associated variable gene segments. We have used recombination substrates comprised of the E mu enhancer together with various lengths of additional downstream mu sequences to assess the individual contribution of those sequences to the V(D)J recombinational regulatory activity. Surprisingly, in the absence of large amounts of mu sequences, substrate rearrangements were not detected in Southern blot analyses of the lymphoid tissues from independent transgenic mice, but were readily detectable following transfection into cultured pre-B cells. A short mu segment which includes matrix association regions (MARs) was not sufficient to restore high levels of rearrangements within the reporter transgenes. However, additional experiments demonstrated that the mu sequences are dispensable for V(D)J recombination in transgenic thymuses, implying a suppressive effect exerted by the vector sequences left in the transgenic insert, when they are attached near the E mu regulatory region. This suppression of V(D)J recombination, which correlates with an hypermethylation of the transgenes, is discussed in view of previously reported transgenic and gene targeting experiments.
Starting Page	1291
Ending Page	1291
Page Count	1
File Format	PDF HTM / HTML
Alternate Webpage(s)	https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/nar/22/5/10.1093/nar/22.5.792/2/22-5-792.pdf?Expires=1493121115&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q&Signature=ZITR0HV5KY8DLuk-acdTK0mTMk5K~~fCZhMB2OXhUbz-3zbDQgiOVuRNJHI4WKiS~-WaPvCCAPjkj3XDoqlpDBx9sRhPAxMrE-KBkK5Baf-IcR-~I9PP0DVmSUBjSjhxN5c9MLdTakMBZZfkJHqG4xOtHdecBYgMZkd1JpE3aoJ-X6Z51yYwM3XqU8BZvypcsjYlrmh-zHRZbFPolEMBGx999LOEWLcYwMzqjqSyHl090qwp4qN~QAymlDl~MRHJGHevCKCUFOb5r1NmimGhQOhne6cHbkAgQrjIdvt1~goFuXjBd4ssOYn48lwEGal~QeebfOTRWpNsY9f9yBQkKA__
PubMed reference number	8139920v1
Volume Number	22
Issue Number	5
Journal	Nucleic acids research
Language	English
Access Restriction	Open
Subject Keyword	Body tissue DNA Sequence Rearrangement Enhancer of transcription Gene Targeting Hypermethylation Immunoglobulin Heavy Chains Introns Lymphoid Tissue Recombination, Genetic Regulatory Sequences, Nucleic Acid SLC3A2 gene T cell receptor V(D)J recombination Transcription, Genetic Transgenes physical hard work
Content Type	Text
Resource Type	Article