Transcription factor YY1 can control AID-mediated mutagenesis in mice

ZÁPRAŽNÁ, Kristína, A. BASU, Nikola TOM, V. JHA, S. HODAWADEKAR, Lenka RADOVÁ, Jitka MALČÍKOVÁ, Boris TICHÝ, Šárka POSPÍŠILOVÁ and M.L. ATCHISON. Transcription factor YY1 can control AID-mediated mutagenesis in mice. Online. EUROPEAN JOURNAL OF IMMUNOLOGY. HOBOKEN: WILEY, 2018, vol. 48, No 2, p. 273-282. ISSN 0014-2980. Available from: https://dx.doi.org/10.1002/eji.201747065. [citováno 2024-04-24]

Basic information

• Original name: Transcription factor YY1 can control AID-mediated mutagenesis in mice
• Authors: ZÁPRAŽNÁ, Kristína (203 Czech Republic, belonging to the institution), A. BASU (840 United States of America), Nikola TOM (203 Czech Republic, belonging to the institution), V. JHA (840 United States of America), S. HODAWADEKAR (840 United States of America), Lenka RADOVÁ (203 Czech Republic, belonging to the institution), Jitka MALČÍKOVÁ (203 Czech Republic, belonging to the institution), Boris TICHÝ (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, guarantor, belonging to the institution) and M.L. ATCHISON (840 United States of America)
• Edition: EUROPEAN JOURNAL OF IMMUNOLOGY, HOBOKEN, WILEY, 2018, 0014-2980.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30102 Immunology
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 4.695
• RIV identification code: RIV/00216224:14740/18:00102362
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1002/eji.201747065
• UT WoS: 000424797700008
• Keywords in English: AID; class switch recombination; somatic hypermutation; YY1
• Tags: CF GEN, rivok
• Tags: International impact, Reviewed

Abstract

Activation-induced cytidine deminase (AID) is crucial for controlling the immunoglobulin (Ig) diversification processes of somatic hypermutation (SHM) and class switch recombination (CSR). AID initiates these processes by deamination of cytosine, ultimately resulting in mutations or double strand DNA breaks needed for SHM and CSR. Levels of AID control mutation rates, and off-target non-Ig gene mutations can contribute to lymphomagenesis. Therefore, factors that control AID levels in the nucleus can regulate SHM and CSR, and may contribute to disease. We previously showed that transcription factor YY1 can regulate the level of AID in the nucleus and Ig CSR. Therefore, we hypothesized that conditional knock-out of YY1 would lead to reduction in AID localization at the Ig locus, and reduced AID-mediated mutations. Using mice that overexpress AID (IgAID yy1(f/f)) or that express normal AID levels (yy1(f/f)), we found that conditional knock-out of YY1 results in reduced AID nuclear levels, reduced localization of AID to the S switch region, and reduced AID-mediated mutations. We find that the mechanism of YY1 control of AID nuclear accumulation is likely due to YY1-AID physical interaction which blocks AID ubiquitination.

Links

• LM2011020, research and development project: Name: CEITEC ? open access

Investor: Ministry of Education, Youth and Sports of the CR

• LQ1601, research and development project: Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

• MUNI/A/1106/2016, interní kód MU: Name: Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit IV (Acronym: VýDiTeHeMA IV)

Investor: Masaryk University, Category A

• 3SGA5792, interní kód MU: Name: Expression and function of activation-induced cytidine deaminase splice variants in normal B cell physiology and chronic lymphocytic leukemia (Acronym: AIDinCLL)

Investor: South-Moravian Region, Incoming grants