Publication Date:
2012-10-02
Description:
Although most genes are expressed biallelically, a number of key genomic sites--including immune and olfactory receptor regions--are controlled monoallelically in a stochastic manner, with some cells expressing the maternal allele and others the paternal allele in the target tissue. Very little is known about how this phenomenon is regulated and programmed during development. Here, using mouse immunoglobulin-kappa (Igkappa) as a model system, we demonstrate that although individual haematopoietic stem cells are characterized by allelic plasticity, early lymphoid lineage cells become committed to the choice of a single allele, and this decision is then stably maintained in a clonal manner that predetermines monoallelic rearrangement in B cells. This is accompanied at the molecular level by underlying allelic changes in asynchronous replication timing patterns at the kappa locus. These experiments may serve to define a new concept of stem cell plasticity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Farago, Marganit -- Rosenbluh, Chaggai -- Tevlin, Maya -- Fraenkel, Shira -- Schlesinger, Sharon -- Masika, Hagit -- Gouzman, Masha -- Teng, Grace -- Schatz, David -- Rais, Yoach -- Hanna, Jacob H -- Mildner, Alexander -- Jung, Steffen -- Mostoslavsky, Gustavo -- Cedar, Howard -- Bergman, Yehudit -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Oct 25;490(7421):561-5. doi: 10.1038/nature11496. Epub 2012 Sep 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University Medical School, POB 12272, Ein Kerem, Jerusalem 91120, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23023124" target="_blank"〉PubMed〈/a〉
Keywords:
*Alleles
;
Animals
;
*Cell Lineage
;
Chromatin Immunoprecipitation
;
Clone Cells/cytology/immunology/metabolism
;
DNA Replication Timing
;
Female
;
Gene Rearrangement, B-Lymphocyte, Light Chain/*genetics
;
Hematopoiesis
;
Humans
;
Immunoglobulin kappa-Chains/*genetics/immunology
;
Male
;
Mice
;
Mice, Inbred BALB C
;
Models, Animal
;
Models, Immunological
;
Precursor Cells, B-Lymphoid/*cytology/immunology/*metabolism
;
Stochastic Processes
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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