Methylation of the promoter region may be involved in tissue-specific expression of the mouse terminal deoxynucleotidyl transferase gene 1 1 Edited by M. Yaniv

Methylation of the promoter region may be involved in tissue-specific expression of the mouse... The terminal deoxynucleotidyl transferase gene ( TdT ) is expressed in mice only in early B and T lymphoid precursors a few days after birth. Transactivating factors have been shown to contribute to the lymphoid specific expression of TdT , but they do not account entirely for the restriction of its expression to early precursors. Since tissue-specific expression can be modulated by other mechanisms such as DNA methylation and DNA accessibility, we evaluated the methylation pattern of the TdT gene in various expressing and non-expressing tissues and cell lines. Lymphoid and non-lymphoid organs differed significantly in their methylation profiles. In the thymus nearly complete demethylation of a Hha I site in the promoter was associated with high levels of TdT transcription. There was similar, but weaker demethylation of the TdT promoter in bone marrow, possibly due to the presence of a few TdT expressing B cell precursors. The same methylation status was also associated with TdT expression in different B and T cell lines. Kinetic studies of TdT gene demethylation and TdT transcription during thymus development showed that changes in methylation status were also involved in the differential expression of TdT in fetal and adult life. Footprinting experiments revealed the existence of three regions specifically protected by nuclear extracts from TdT -expressing cells. Together, these results suggest that promoter demethylation is involved in the control of TdT expression and implicate new promoter regions in this regulation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Molecular Biology Elsevier

Methylation of the promoter region may be involved in tissue-specific expression of the mouse terminal deoxynucleotidyl transferase gene 1 1 Edited by M. Yaniv

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Publisher
Elsevier
Copyright
Copyright © 1999 Academic Press
ISSN
0022-2836
DOI
10.1006/jmbi.1999.3079
Publisher site
See Article on Publisher Site

Abstract

The terminal deoxynucleotidyl transferase gene ( TdT ) is expressed in mice only in early B and T lymphoid precursors a few days after birth. Transactivating factors have been shown to contribute to the lymphoid specific expression of TdT , but they do not account entirely for the restriction of its expression to early precursors. Since tissue-specific expression can be modulated by other mechanisms such as DNA methylation and DNA accessibility, we evaluated the methylation pattern of the TdT gene in various expressing and non-expressing tissues and cell lines. Lymphoid and non-lymphoid organs differed significantly in their methylation profiles. In the thymus nearly complete demethylation of a Hha I site in the promoter was associated with high levels of TdT transcription. There was similar, but weaker demethylation of the TdT promoter in bone marrow, possibly due to the presence of a few TdT expressing B cell precursors. The same methylation status was also associated with TdT expression in different B and T cell lines. Kinetic studies of TdT gene demethylation and TdT transcription during thymus development showed that changes in methylation status were also involved in the differential expression of TdT in fetal and adult life. Footprinting experiments revealed the existence of three regions specifically protected by nuclear extracts from TdT -expressing cells. Together, these results suggest that promoter demethylation is involved in the control of TdT expression and implicate new promoter regions in this regulation.

Journal

Journal of Molecular BiologyElsevier

Published: Sep 17, 1999

References

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    Feeney, A.J.
  • Transcriptional regulation of T lymphocyte development and function
    Kuo, C.T.; Leiden, J.M.
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    Li, Y.S.; Hayakawa, K.; Hardy, R.R.
  • Antigen receptor engagement turns off the V(D)J recombination machinery in human tonsil B cells
    Meffre, E.; Papavasiliou, F.; Cohen, P.; Bouteiller de, O.; Bell, D.; Karasuyama, H.; Schiff, C.; Banchereau, J.; Liu, Y.J.; Nussenzweig, M.C.
  • CpG methylation, chromatin structure and gene silencing- a three way connection
    Razin, A.
  • Molecular Cloning
    Sambrook, J.; Fritsch, E.F.; Maniatis, T.
  • Early T lymphocyte progenitors
    Shortman, K.; Wu, L.

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