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ETS1 and PAX5 transcription factors recruit AID to Igh DNA
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
Vise andre og tillknytning
2018 (engelsk)Inngår i: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 48, nr 10, s. 1687-1697Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

B lymphocytes optimize antibody responses by class switch recombination (CSR), which changes the expressed constant region exon of the immunoglobulin heavy chain (IgH), and by somatic hypermutation (SH) that introduces point mutations in the variable regions of the antibody genes. Activation-induced cytidine deaminase (AID) is the key mutagenic enzyme that initiates both these antibody diversification processes by deaminating cytosine to uracil. Here we asked the question if transcription factors can mediate the specific targeting of the antibody diversification by recruiting AID. We have recently reported that AID is together with the transcription factors E2A, PAX5 and IRF4 in a complex on key sequences of the Igh locus. Here we report that also ETS1 is together with AID in this complex on key sequences of the Igh locus in splenic B cells of mice. Furthermore, we show that both ETS1 and PAX5 can directly recruit AID to DNA sequences from the Igh locus with the specific binding site for the transcription factor. Taken together, our findings support the notion of a targeting mechanism for the selective diversification of antibody genes with limited genome wide mutagenesis by recruitment of AID by PAX5 and ETS1 in a transcription factor complex.

sted, utgiver, år, opplag, sider
Wiley-VCH Verlagsgesellschaft, 2018. Vol. 48, nr 10, s. 1687-1697
Emneord [en]
Activation-induced cytidine deaminase, Class switch recombination, Protein interactions, Somatic hypermutation, Transcription factors
HSV kategori
Identifikatorer
URN: urn:nbn:se:umu:diva-152886DOI: 10.1002/eji.201847625ISI: 000446431600008PubMedID: 30089192OAI: oai:DiVA.org:umu-152886DiVA, id: diva2:1259819
Forskningsfinansiär
Swedish Cancer SocietySwedish Research CouncilTilgjengelig fra: 2018-10-31 Laget: 2018-10-31 Sist oppdatert: 2018-10-31bibliografisk kontrollert

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