TY - JOUR
T1 - Inducible CTCF insulator delays the IgH 3' regulatory region-mediated activation of germline promoters and alters class switching
AU - Braikia, Fatima Zohra
AU - Oudinet, Chloé
AU - Haddad, Dania
AU - Oruc, Zeliha
AU - Orlando, Domenico
AU - Dauba, Audrey
AU - Le Bert, Marc L.
AU - Khamlichi, Ahmed Amine
PY - 2017/6/6
Y1 - 2017/6/6
N2 - Class switch recombination (CSR) plays an important role in adaptive immune response by enabling mature B cells to switch from IgM expression to the expression of downstream isotypes. CSR is preceded by inducible germline (GL) transcription of the constant genes and is controlled by the 3' regulatory region (3'RR) in a stimulus-dependent manner. Why the 3'RR-mediated upregulation of GL transcription is delayed to the mature B-cell stage is presently unknown. Here we show that mice devoid of an inducible CTCF binding element, located in the a constant gene, display a marked isotype-specific increase of GL transcription in developing and resting splenic B cells and altered CSR in activated B cells. Moreover, insertion of a GL promoter downstream of the CTCF insulator led to premature activation of the ectopic promoter. This study provides functional evidence that the 3'RR has a developmentally controlled potential to constitutively activate GL promoters but that this activity is delayed, at least in part, by the CTCF insulator, which borders a transcriptionally active domain established by the 3'RR in developing B cells.
AB - Class switch recombination (CSR) plays an important role in adaptive immune response by enabling mature B cells to switch from IgM expression to the expression of downstream isotypes. CSR is preceded by inducible germline (GL) transcription of the constant genes and is controlled by the 3' regulatory region (3'RR) in a stimulus-dependent manner. Why the 3'RR-mediated upregulation of GL transcription is delayed to the mature B-cell stage is presently unknown. Here we show that mice devoid of an inducible CTCF binding element, located in the a constant gene, display a marked isotype-specific increase of GL transcription in developing and resting splenic B cells and altered CSR in activated B cells. Moreover, insertion of a GL promoter downstream of the CTCF insulator led to premature activation of the ectopic promoter. This study provides functional evidence that the 3'RR has a developmentally controlled potential to constitutively activate GL promoters but that this activity is delayed, at least in part, by the CTCF insulator, which borders a transcriptionally active domain established by the 3'RR in developing B cells.
KW - B lymphocyte
KW - Class switch recombination
KW - Germline transcription
KW - IgH locus
KW - Insulator
UR - http://www.scopus.com/inward/record.url?scp=85020316347&partnerID=8YFLogxK
U2 - 10.1073/pnas.1701631114
DO - 10.1073/pnas.1701631114
M3 - Article
C2 - 28533409
AN - SCOPUS:85020316347
VL - 114
SP - 6092
EP - 6097
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 23
ER -