A PTIP-PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Standard

A PTIP-PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex. / Starnes, Linda M; Su, Dan; Pikkupeura, Laura M; Weinert, Brian T; Santos, Margarida A; Mund, Andreas; Soria, Rebeca; Cho, Young-Wook; Pozdnyakova, Irina; Kubec Højfeldt, Martina; Vala, Andrea; Yang, Wenjing; López-Méndez, Blanca; Lee, Ji-Eun; Peng, Weiqun; Yuan, Joan; Ge, Kai; Montoya, Guillermo; Nussenzweig, André; Choudhary, Chunaram; Daniel, Jeremy A.

I: Genes & Development, Vol. 30, Nr. 2, 2016, s. 149-163.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Starnes, LM, Su, D, Pikkupeura, LM, Weinert, BT, Santos, MA, Mund, A, Soria, R, Cho, Y-W, Pozdnyakova, I, Kubec Højfeldt, M, Vala, A, Yang, W, López-Méndez, B, Lee, J-E, Peng, W, Yuan, J, Ge, K, Montoya, G, Nussenzweig, A, Choudhary, C & Daniel, JA 2016, 'A PTIP-PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex.', Genes & Development, vol. 30, nr. 2, s. 149-163. https://doi.org/10.1101/gad.268797.115

APA

CBE

Starnes LM, Su D, Pikkupeura LM, Weinert BT, Santos MA, Mund A, Soria R, Cho Y-W, Pozdnyakova I, Kubec Højfeldt M, Vala A, Yang W, López-Méndez B, Lee J-E, Peng W, Yuan J, Ge K, Montoya G, Nussenzweig A, Choudhary C, Daniel JA. 2016. A PTIP-PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex. Genes & Development. 30(2):149-163. https://doi.org/10.1101/gad.268797.115

MLA

Vancouver

Author

Starnes, Linda M ; Su, Dan ; Pikkupeura, Laura M ; Weinert, Brian T ; Santos, Margarida A ; Mund, Andreas ; Soria, Rebeca ; Cho, Young-Wook ; Pozdnyakova, Irina ; Kubec Højfeldt, Martina ; Vala, Andrea ; Yang, Wenjing ; López-Méndez, Blanca ; Lee, Ji-Eun ; Peng, Weiqun ; Yuan, Joan ; Ge, Kai ; Montoya, Guillermo ; Nussenzweig, André ; Choudhary, Chunaram ; Daniel, Jeremy A. / A PTIP-PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex. I: Genes & Development. 2016 ; Vol. 30, Nr. 2. s. 149-163.

RIS

TY - JOUR

T1 - A PTIP-PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex.

AU - Starnes, Linda M

AU - Su, Dan

AU - Pikkupeura, Laura M

AU - Weinert, Brian T

AU - Santos, Margarida A

AU - Mund, Andreas

AU - Soria, Rebeca

AU - Cho, Young-Wook

AU - Pozdnyakova, Irina

AU - Kubec Højfeldt, Martina

AU - Vala, Andrea

AU - Yang, Wenjing

AU - López-Méndez, Blanca

AU - Lee, Ji-Eun

AU - Peng, Weiqun

AU - Yuan, Joan

AU - Ge, Kai

AU - Montoya, Guillermo

AU - Nussenzweig, André

AU - Choudhary, Chunaram

AU - Daniel, Jeremy A

PY - 2016

Y1 - 2016

N2 - Class switch recombination (CSR) diversifies antibodies for productive immune responses while maintaining stability of the B-cell genome. Transcription at the immunoglobulin heavy chain (Igh) locus targets CSR-associated DNA damage and is promoted by the BRCT domain-containing PTIP (Pax transactivation domain-interacting protein). Although PTIP is a unique component of the mixed-lineage leukemia 3 (MLL3)/MLL4 chromatin-modifying complex, the mechanisms for how PTIP promotes transcription remain unclear. Here we dissected the minimal structural requirements of PTIP and its different protein complexes using quantitative proteomics in primary lymphocytes. We found that PTIP functions in transcription and CSR separately from its association with the MLL3/MLL4 complex and from its localization to sites of DNA damage. We identified a tandem BRCT domain of PTIP that is sufficient for CSR and identified PA1 as its main functional protein partner. Collectively, we provide genetic and biochemical evidence that a PTIP-PA1 subcomplex functions independently from the MLL3/MLL4 complex to mediate transcription during CSR. These results further our understanding of how multifunctional chromatin-modifying complexes are organized by subcomplexes that harbor unique and distinct activities.

AB - Class switch recombination (CSR) diversifies antibodies for productive immune responses while maintaining stability of the B-cell genome. Transcription at the immunoglobulin heavy chain (Igh) locus targets CSR-associated DNA damage and is promoted by the BRCT domain-containing PTIP (Pax transactivation domain-interacting protein). Although PTIP is a unique component of the mixed-lineage leukemia 3 (MLL3)/MLL4 chromatin-modifying complex, the mechanisms for how PTIP promotes transcription remain unclear. Here we dissected the minimal structural requirements of PTIP and its different protein complexes using quantitative proteomics in primary lymphocytes. We found that PTIP functions in transcription and CSR separately from its association with the MLL3/MLL4 complex and from its localization to sites of DNA damage. We identified a tandem BRCT domain of PTIP that is sufficient for CSR and identified PA1 as its main functional protein partner. Collectively, we provide genetic and biochemical evidence that a PTIP-PA1 subcomplex functions independently from the MLL3/MLL4 complex to mediate transcription during CSR. These results further our understanding of how multifunctional chromatin-modifying complexes are organized by subcomplexes that harbor unique and distinct activities.

U2 - 10.1101/gad.268797.115

DO - 10.1101/gad.268797.115

M3 - Article

VL - 30

SP - 149

EP - 163

JO - Genes and Development

JF - Genes and Development

SN - 1549-5477

IS - 2

ER -