J 2018

Transcription factor YY1 can control AID-mediated mutagenesis in mice

ZÁPRAŽNÁ, Kristína, A. BASU, Nikola TOM, V. JHA, S. HODAWADEKAR et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30102 Immunology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 4.695

RIV identification code

RIV/00216224:14740/18:00102362

Organization unit

Central European Institute of Technology

DOI

UT WoS

000424797700008

Keywords in English

AID; class switch recombination; somatic hypermutation; YY1

Tags

Tags

International impact, Reviewed
Změněno: 13/3/2019 17:23, Mgr. Pavla Foltynová, Ph.D.

Abstract

V originále

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