53BP1 contributes to igh locus chromatin topology during class switch recombination

Scott Feldman, Robert Wuerffel, Ikbel Achour, Lili Wang, Phillip B. Carpenter, Amy L. Kenter

Research output: Contribution to journalArticle

  • 1 Citations

Abstract

In B lymphocytes, Ig class switch recombination (CSR) is induced by activation-induced cytidine deaminase, which initiates a cascade of events leading to DNA double-strand break formation in switch (S) regions. Resolution of DNA double-strand breaks proceeds through formation of S-S synaptic complexes. S-S synapsis is mediated by a chromatin loop that spans the C region domain of the Igh locus. S-S junctions are joined via a nonhomologous end joining DNA repair process. CSR occurs via an intrachromosomal looping out and deletion mechanism that is 53BP1 dependent. However, the mechanism by which 53BP1 facilitates deletional CSR and inhibits inversional switching events remains unknown. We report a novel architectural role for 53BP1 in Igh chromatin looping in mouse B cells. Long-range interactions between the Em and 39Ea enhancers are significantly diminished in the absence of 53BP1. In contrast, germline transcript promoter:39Ea looping interactions are unaffected by 53BP1 deficiency. Furthermore, 53BP1 chromatin occupancy at sites in the Igh locus is B cell specific, is correlated with histone H4 lysine 20 marks, and is subject to chromatin spreading. Thus, 53BP1 is required for three-dimensional organization of the Igh locus and provides a plausible explanation for the link with 53BP1 enforcement of deletional CSR.

Original languageEnglish (US)
Pages (from-to)2434-2444
Number of pages11
JournalJournal of Immunology
Volume198
Issue number6
DOIs
StatePublished - Mar 15 2017

Fingerprint

Genetic Recombination
Chromatin
B-Lymphocytes
DNA End-Joining Repair
Double-Stranded DNA Breaks
Cytidine Deaminase
Chromosome Pairing
Histones
Lysine

ASJC Scopus subject areas

  • Immunology

Cite this

Feldman, S., Wuerffel, R., Achour, I., Wang, L., Carpenter, P. B., & Kenter, A. L. (2017). 53BP1 contributes to igh locus chromatin topology during class switch recombination. Journal of Immunology, 198(6), 2434-2444. DOI: 10.4049/jimmunol.1601947

53BP1 contributes to igh locus chromatin topology during class switch recombination. / Feldman, Scott; Wuerffel, Robert; Achour, Ikbel; Wang, Lili; Carpenter, Phillip B.; Kenter, Amy L.

In: Journal of Immunology, Vol. 198, No. 6, 15.03.2017, p. 2434-2444.

Research output: Contribution to journalArticle

Feldman, S, Wuerffel, R, Achour, I, Wang, L, Carpenter, PB & Kenter, AL 2017, '53BP1 contributes to igh locus chromatin topology during class switch recombination' Journal of Immunology, vol 198, no. 6, pp. 2434-2444. DOI: 10.4049/jimmunol.1601947
Feldman S, Wuerffel R, Achour I, Wang L, Carpenter PB, Kenter AL. 53BP1 contributes to igh locus chromatin topology during class switch recombination. Journal of Immunology. 2017 Mar 15;198(6):2434-2444. Available from, DOI: 10.4049/jimmunol.1601947

Feldman, Scott; Wuerffel, Robert; Achour, Ikbel; Wang, Lili; Carpenter, Phillip B.; Kenter, Amy L. / 53BP1 contributes to igh locus chromatin topology during class switch recombination.

In: Journal of Immunology, Vol. 198, No. 6, 15.03.2017, p. 2434-2444.

Research output: Contribution to journalArticle

@article{9d5afe0074694511bc13bd759d6af609,
title = "53BP1 contributes to igh locus chromatin topology during class switch recombination",
abstract = "In B lymphocytes, Ig class switch recombination (CSR) is induced by activation-induced cytidine deaminase, which initiates a cascade of events leading to DNA double-strand break formation in switch (S) regions. Resolution of DNA double-strand breaks proceeds through formation of S-S synaptic complexes. S-S synapsis is mediated by a chromatin loop that spans the C region domain of the Igh locus. S-S junctions are joined via a nonhomologous end joining DNA repair process. CSR occurs via an intrachromosomal looping out and deletion mechanism that is 53BP1 dependent. However, the mechanism by which 53BP1 facilitates deletional CSR and inhibits inversional switching events remains unknown. We report a novel architectural role for 53BP1 in Igh chromatin looping in mouse B cells. Long-range interactions between the Em and 39Ea enhancers are significantly diminished in the absence of 53BP1. In contrast, germline transcript promoter:39Ea looping interactions are unaffected by 53BP1 deficiency. Furthermore, 53BP1 chromatin occupancy at sites in the Igh locus is B cell specific, is correlated with histone H4 lysine 20 marks, and is subject to chromatin spreading. Thus, 53BP1 is required for three-dimensional organization of the Igh locus and provides a plausible explanation for the link with 53BP1 enforcement of deletional CSR.",
author = "Scott Feldman and Robert Wuerffel and Ikbel Achour and Lili Wang and Carpenter, {Phillip B.} and Kenter, {Amy L.}",
year = "2017",
month = "3",
doi = "10.4049/jimmunol.1601947",
volume = "198",
pages = "2434--2444",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

TY - JOUR

T1 - 53BP1 contributes to igh locus chromatin topology during class switch recombination

AU - Feldman,Scott

AU - Wuerffel,Robert

AU - Achour,Ikbel

AU - Wang,Lili

AU - Carpenter,Phillip B.

AU - Kenter,Amy L.

PY - 2017/3/15

Y1 - 2017/3/15

N2 - In B lymphocytes, Ig class switch recombination (CSR) is induced by activation-induced cytidine deaminase, which initiates a cascade of events leading to DNA double-strand break formation in switch (S) regions. Resolution of DNA double-strand breaks proceeds through formation of S-S synaptic complexes. S-S synapsis is mediated by a chromatin loop that spans the C region domain of the Igh locus. S-S junctions are joined via a nonhomologous end joining DNA repair process. CSR occurs via an intrachromosomal looping out and deletion mechanism that is 53BP1 dependent. However, the mechanism by which 53BP1 facilitates deletional CSR and inhibits inversional switching events remains unknown. We report a novel architectural role for 53BP1 in Igh chromatin looping in mouse B cells. Long-range interactions between the Em and 39Ea enhancers are significantly diminished in the absence of 53BP1. In contrast, germline transcript promoter:39Ea looping interactions are unaffected by 53BP1 deficiency. Furthermore, 53BP1 chromatin occupancy at sites in the Igh locus is B cell specific, is correlated with histone H4 lysine 20 marks, and is subject to chromatin spreading. Thus, 53BP1 is required for three-dimensional organization of the Igh locus and provides a plausible explanation for the link with 53BP1 enforcement of deletional CSR.

AB - In B lymphocytes, Ig class switch recombination (CSR) is induced by activation-induced cytidine deaminase, which initiates a cascade of events leading to DNA double-strand break formation in switch (S) regions. Resolution of DNA double-strand breaks proceeds through formation of S-S synaptic complexes. S-S synapsis is mediated by a chromatin loop that spans the C region domain of the Igh locus. S-S junctions are joined via a nonhomologous end joining DNA repair process. CSR occurs via an intrachromosomal looping out and deletion mechanism that is 53BP1 dependent. However, the mechanism by which 53BP1 facilitates deletional CSR and inhibits inversional switching events remains unknown. We report a novel architectural role for 53BP1 in Igh chromatin looping in mouse B cells. Long-range interactions between the Em and 39Ea enhancers are significantly diminished in the absence of 53BP1. In contrast, germline transcript promoter:39Ea looping interactions are unaffected by 53BP1 deficiency. Furthermore, 53BP1 chromatin occupancy at sites in the Igh locus is B cell specific, is correlated with histone H4 lysine 20 marks, and is subject to chromatin spreading. Thus, 53BP1 is required for three-dimensional organization of the Igh locus and provides a plausible explanation for the link with 53BP1 enforcement of deletional CSR.

UR - http://www.scopus.com/inward/record.url?scp=85014731158&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014731158&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1601947

DO - 10.4049/jimmunol.1601947

M3 - Article

VL - 198

SP - 2434

EP - 2444

JO - Journal of Immunology

T2 - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -