Ikaros and RAG-2-mediated antisense transcription are responsible for lymphocyte-specific inactivation of NWC promoter.

Recombination activating gene-2 (RAG-2) and NWC are strongly evolutionarily conserved overlapping genes which are convergently transcribed. In non-lymphoid cells the NWC promoter is active whereas in lymphocytes it is inactive due to the DNA methylation. Analysing the mechanism responsible for lymph...

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Main Authors: Agnieszka Laszkiewicz, Łukasz Bzdzion, Monika Kasztura, Lukasz Snieżewski, Sylwia Janik, Paweł Kisielow, Małgorzata Cebrat
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4157847?pdf=render
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author Agnieszka Laszkiewicz
Łukasz Bzdzion
Monika Kasztura
Lukasz Snieżewski
Sylwia Janik
Paweł Kisielow
Małgorzata Cebrat
author_facet Agnieszka Laszkiewicz
Łukasz Bzdzion
Monika Kasztura
Lukasz Snieżewski
Sylwia Janik
Paweł Kisielow
Małgorzata Cebrat
author_sort Agnieszka Laszkiewicz
collection DOAJ
description Recombination activating gene-2 (RAG-2) and NWC are strongly evolutionarily conserved overlapping genes which are convergently transcribed. In non-lymphoid cells the NWC promoter is active whereas in lymphocytes it is inactive due to the DNA methylation. Analysing the mechanism responsible for lymphocyte-specific methylation and inactivation of NWC promoter we found that Ikaros, a lymphocyte-specific transcription factor, acts as a repressor of NWC promoter--thus identifying a new Ikaros target--but is insufficient for inducing its methylation which depends on the antisense transcription driven by RAG-2 promoter. Possible implications of these observations for understanding evolutionary mechanisms leading to lymphocyte specific expression of RAG genes are discussed.
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spelling doaj.art-255cccf305694eef882d4f0ac2b30bee2022-12-22T00:19:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10692710.1371/journal.pone.0106927Ikaros and RAG-2-mediated antisense transcription are responsible for lymphocyte-specific inactivation of NWC promoter.Agnieszka LaszkiewiczŁukasz BzdzionMonika KaszturaLukasz SnieżewskiSylwia JanikPaweł KisielowMałgorzata CebratRecombination activating gene-2 (RAG-2) and NWC are strongly evolutionarily conserved overlapping genes which are convergently transcribed. In non-lymphoid cells the NWC promoter is active whereas in lymphocytes it is inactive due to the DNA methylation. Analysing the mechanism responsible for lymphocyte-specific methylation and inactivation of NWC promoter we found that Ikaros, a lymphocyte-specific transcription factor, acts as a repressor of NWC promoter--thus identifying a new Ikaros target--but is insufficient for inducing its methylation which depends on the antisense transcription driven by RAG-2 promoter. Possible implications of these observations for understanding evolutionary mechanisms leading to lymphocyte specific expression of RAG genes are discussed.http://europepmc.org/articles/PMC4157847?pdf=render
spellingShingle Agnieszka Laszkiewicz
Łukasz Bzdzion
Monika Kasztura
Lukasz Snieżewski
Sylwia Janik
Paweł Kisielow
Małgorzata Cebrat
Ikaros and RAG-2-mediated antisense transcription are responsible for lymphocyte-specific inactivation of NWC promoter.
PLoS ONE
title Ikaros and RAG-2-mediated antisense transcription are responsible for lymphocyte-specific inactivation of NWC promoter.
title_full Ikaros and RAG-2-mediated antisense transcription are responsible for lymphocyte-specific inactivation of NWC promoter.
title_fullStr Ikaros and RAG-2-mediated antisense transcription are responsible for lymphocyte-specific inactivation of NWC promoter.
title_full_unstemmed Ikaros and RAG-2-mediated antisense transcription are responsible for lymphocyte-specific inactivation of NWC promoter.
title_short Ikaros and RAG-2-mediated antisense transcription are responsible for lymphocyte-specific inactivation of NWC promoter.
title_sort ikaros and rag 2 mediated antisense transcription are responsible for lymphocyte specific inactivation of nwc promoter
url http://europepmc.org/articles/PMC4157847?pdf=render
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