期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 434, 期 7, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2022.167509
关键词
nuclear organization; Chromosome territory; enhancers; chromatin organization; VDJ recombination
资金
- NII
- Department of Biotechnology, Government of India
The intranuclear position of the TCRb locus is dynamically altered during thymic development and is influenced by the enhancer Eb. The ability to reposition the target locus relative to the chromosome territory highlights a novel aspect of enhancer activity, which may contribute to gene expression regulation. These observations have implications for understanding enhancer function in three-dimensional genome organization.
Intranuclear position of several genes is dynamically altered during development concordant with their activation. To understand this dynamic, but non-random, nuclear organization, it is important to identify the relevant regulatory elements and trans acting factors. Murine TCRb locus gets activated during thymic development. Enhancer Eb is important for VDJ recombination at TCRb locus as it is critically required for establishment of recombination center. Our analysis revealed that TCRb locus gets located out of the chromosome territory specifically in developing thymocytes. Further, CRISPR/Cas9 based deletion mutagenesis established an unambiguous role of enhancer Eb in defining TCRb location relative to chromosome territory. The ability to reposition the target locus relative to chromosome territory highlights a novel aspect pertaining to activity of enhancers which may contribute to their ability to regulate gene expression. Additionally, our observations have implications for understanding the role of enhancers in three-dimensional genome organization and function.(c) 2022 Elsevier Ltd. All rights reserved.
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