Flexible long-range loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire

J. Medvedovic; A. Ebert; H. Tagoh; I.M. Tamir; T.A. Schwickert; M. Novatchkova; Q. Sun; P.J. Huis In 't Veld; C. Guo; H.S. Yoon; Y. Denizot; S.J. Holwerda; W. de Laat; M. Cogne; Y. Shi; F.W. Alt; M. Busslinger

doi:10.1016/j.immuni.2013.08.011

Flexible long-range loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire

J. Medvedovic, A. Ebert, H. Tagoh, I.M. Tamir, T.A. Schwickert, M. Novatchkova, Q. Sun, P.J. Huis In 't Veld, C. Guo, H.S. Yoon, Y. Denizot, S.J. Holwerda, W. de Laat, M. Cogne, Y. Shi, F.W. Alt, M. Busslinger

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

118 Citaten (Scopus)

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The immunoglobulin heavy-chain (Igh) locus undergoes large-scale contraction in pro-B cells, which facilitates VH-DJH recombination by juxtaposing distal VH genes next to the DJH-rearranged gene segment in the 3' proximal Igh domain. By using high-resolution mapping of long-range interactions, we demonstrate that local interaction domains established the three-dimensional structure of the extended Igh locus in lymphoid progenitors. In pro-B cells, these local domains engaged in long-range interactions across the Igh locus, which depend on the regulators Pax5, YY1, and CTCF. The large VH gene cluster underwent flexible long-range interactions with the more rigidly structured proximal domain, which probably ensures similar participation of all VH genes in VH-DJH recombination to generate a diverse antibody repertoire. These long-range interactions appear to be an intrinsic feature of the VH gene cluster, because they are still generated upon mutation of the Emu enhancer, IGCR1 insulator, or 3' regulatory region in the proximal Igh domain.

Originele taal-2	Engels
Pagina's (van-tot)	229-244
Tijdschrift	Immunity
Volume	39
Nummer van het tijdschrift	2
DOI's	https://doi.org/10.1016/j.immuni.2013.08.011
Status	Gepubliceerd - 2013

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10.1016/j.immuni.2013.08.011

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Medvedovic, J., Ebert, A., Tagoh, H., Tamir, I. M., Schwickert, T. A., Novatchkova, M., Sun, Q., Huis In 't Veld, P. J., Guo, C., Yoon, H. S., Denizot, Y., Holwerda, S. J., de Laat, W., Cogne, M., Shi, Y., Alt, F. W., & Busslinger, M. (2013). Flexible long-range loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire. Immunity, 39(2), 229-244. https://doi.org/10.1016/j.immuni.2013.08.011

@article{d001b2f998c34cd6a210d3aa82fd96fa,

title = "Flexible long-range loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire",

abstract = "The immunoglobulin heavy-chain (Igh) locus undergoes large-scale contraction in pro-B cells, which facilitates VH-DJH recombination by juxtaposing distal VH genes next to the DJH-rearranged gene segment in the 3' proximal Igh domain. By using high-resolution mapping of long-range interactions, we demonstrate that local interaction domains established the three-dimensional structure of the extended Igh locus in lymphoid progenitors. In pro-B cells, these local domains engaged in long-range interactions across the Igh locus, which depend on the regulators Pax5, YY1, and CTCF. The large VH gene cluster underwent flexible long-range interactions with the more rigidly structured proximal domain, which probably ensures similar participation of all VH genes in VH-DJH recombination to generate a diverse antibody repertoire. These long-range interactions appear to be an intrinsic feature of the VH gene cluster, because they are still generated upon mutation of the Emu enhancer, IGCR1 insulator, or 3' regulatory region in the proximal Igh domain.",

author = "J. Medvedovic and A. Ebert and H. Tagoh and I.M. Tamir and T.A. Schwickert and M. Novatchkova and Q. Sun and {Huis In 't Veld}, P.J. and C. Guo and H.S. Yoon and Y. Denizot and S.J. Holwerda and {de Laat}, W. and M. Cogne and Y. Shi and F.W. Alt and M. Busslinger",

note = "Reporting year: 2013",

year = "2013",

doi = "10.1016/j.immuni.2013.08.011",

language = "English",

volume = "39",

pages = "229--244",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "2",

}

Medvedovic, J, Ebert, A, Tagoh, H, Tamir, IM, Schwickert, TA, Novatchkova, M, Sun, Q, Huis In 't Veld, PJ, Guo, C, Yoon, HS, Denizot, Y, Holwerda, SJ, de Laat, W, Cogne, M, Shi, Y, Alt, FW & Busslinger, M 2013, 'Flexible long-range loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire', Immunity, vol. 39, nr. 2, blz. 229-244. https://doi.org/10.1016/j.immuni.2013.08.011

TY - JOUR

T1 - Flexible long-range loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire

AU - Medvedovic, J.

AU - Ebert, A.

AU - Tagoh, H.

AU - Tamir, I.M.

AU - Schwickert, T.A.

AU - Novatchkova, M.

AU - Sun, Q.

AU - Huis In 't Veld, P.J.

AU - Guo, C.

AU - Yoon, H.S.

AU - Denizot, Y.

AU - Holwerda, S.J.

AU - de Laat, W.

AU - Cogne, M.

AU - Shi, Y.

AU - Alt, F.W.

AU - Busslinger, M.

N1 - Reporting year: 2013

PY - 2013

Y1 - 2013

N2 - The immunoglobulin heavy-chain (Igh) locus undergoes large-scale contraction in pro-B cells, which facilitates VH-DJH recombination by juxtaposing distal VH genes next to the DJH-rearranged gene segment in the 3' proximal Igh domain. By using high-resolution mapping of long-range interactions, we demonstrate that local interaction domains established the three-dimensional structure of the extended Igh locus in lymphoid progenitors. In pro-B cells, these local domains engaged in long-range interactions across the Igh locus, which depend on the regulators Pax5, YY1, and CTCF. The large VH gene cluster underwent flexible long-range interactions with the more rigidly structured proximal domain, which probably ensures similar participation of all VH genes in VH-DJH recombination to generate a diverse antibody repertoire. These long-range interactions appear to be an intrinsic feature of the VH gene cluster, because they are still generated upon mutation of the Emu enhancer, IGCR1 insulator, or 3' regulatory region in the proximal Igh domain.

AB - The immunoglobulin heavy-chain (Igh) locus undergoes large-scale contraction in pro-B cells, which facilitates VH-DJH recombination by juxtaposing distal VH genes next to the DJH-rearranged gene segment in the 3' proximal Igh domain. By using high-resolution mapping of long-range interactions, we demonstrate that local interaction domains established the three-dimensional structure of the extended Igh locus in lymphoid progenitors. In pro-B cells, these local domains engaged in long-range interactions across the Igh locus, which depend on the regulators Pax5, YY1, and CTCF. The large VH gene cluster underwent flexible long-range interactions with the more rigidly structured proximal domain, which probably ensures similar participation of all VH genes in VH-DJH recombination to generate a diverse antibody repertoire. These long-range interactions appear to be an intrinsic feature of the VH gene cluster, because they are still generated upon mutation of the Emu enhancer, IGCR1 insulator, or 3' regulatory region in the proximal Igh domain.

U2 - 10.1016/j.immuni.2013.08.011

DO - 10.1016/j.immuni.2013.08.011

M3 - Article

SN - 1074-7613

VL - 39

SP - 229

EP - 244

JO - Immunity

JF - Immunity

IS - 2

ER -

Flexible long-range loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire

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