Symplekin, a polyadenylation factor, prevents MOZ and MLL activity on HOXA9 in hematopoietic cells

Anne Largeot; Jérôme Paggetti; Julien Broséus; Romain Aucagne; Brice Lagrange; Romain Z. Martin; Jean Berthelet; Ronan Quéré; Géraldine Lucchi; Patrick Ducoroy; Jean Noël Bastie; Laurent Delva

doi:10.1016/j.bbamcr.2013.08.013

Symplekin, a polyadenylation factor, prevents MOZ and MLL activity on HOXA9 in hematopoietic cells

Anne Largeot, Jérôme Paggetti, Julien Broséus, Romain Aucagne, Brice Lagrange, Romain Z. Martin, Jean Berthelet, Ronan Quéré, Géraldine Lucchi, Patrick Ducoroy, Jean Noël Bastie, Laurent Delva^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

4 Citations (Scopus)

Abstract

MOZ and MLL encoding a histone acetyltransferase and a histone methyltransferase, respectively, are targets for recurrent chromosomal translocations found in acute myeloblastic or lymphoblastic leukemia. We have previously shown that MOZ and MLL cooperate to activate HOXA9 gene expression in hematopoietic stem/progenitors cells. To dissect the mechanism of action of this complex, we decided to identify new proteins interacting with MOZ. We found that the scaffold protein Symplekin that supports the assembly of polyadenylation machinery was identified by mass spectrometry. Symplekin interacts and co-localizes with both MOZ and MLL in immature hematopoietic cells. Its inhibition leads to a decrease of the HOXA9 protein level but not of Hoxa9 mRNA and to an over-recruitment of MOZ and MLL onto the HOXA9 promoter. Altogether, our results highlight the role of Symplekin in transcription repression involving a regulatory network between MOZ, MLL and Symplekin.

Original language	English
Pages (from-to)	3054-3063
Number of pages	10
Journal	Biochimica et Biophysica Acta - Molecular Cell Research
Volume	1833
Issue number	12
DOIs	https://doi.org/10.1016/j.bbamcr.2013.08.013
Publication status	Published - Dec 2013

Keywords

HOXA9
MLL
MOZ
Symplekin
Transcription regulation

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10.1016/j.bbamcr.2013.08.013

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Largeot, A., Paggetti, J., Broséus, J., Aucagne, R., Lagrange, B., Martin, R. Z., Berthelet, J., Quéré, R., Lucchi, G., Ducoroy, P., Bastie, J. N., & Delva, L. (2013). Symplekin, a polyadenylation factor, prevents MOZ and MLL activity on HOXA9 in hematopoietic cells. Biochimica et Biophysica Acta - Molecular Cell Research, 1833(12), 3054-3063. https://doi.org/10.1016/j.bbamcr.2013.08.013

@article{08d1d5d3e4904d07b988b9a23977c92b,

title = "Symplekin, a polyadenylation factor, prevents MOZ and MLL activity on HOXA9 in hematopoietic cells",

abstract = "MOZ and MLL encoding a histone acetyltransferase and a histone methyltransferase, respectively, are targets for recurrent chromosomal translocations found in acute myeloblastic or lymphoblastic leukemia. We have previously shown that MOZ and MLL cooperate to activate HOXA9 gene expression in hematopoietic stem/progenitors cells. To dissect the mechanism of action of this complex, we decided to identify new proteins interacting with MOZ. We found that the scaffold protein Symplekin that supports the assembly of polyadenylation machinery was identified by mass spectrometry. Symplekin interacts and co-localizes with both MOZ and MLL in immature hematopoietic cells. Its inhibition leads to a decrease of the HOXA9 protein level but not of Hoxa9 mRNA and to an over-recruitment of MOZ and MLL onto the HOXA9 promoter. Altogether, our results highlight the role of Symplekin in transcription repression involving a regulatory network between MOZ, MLL and Symplekin.",

keywords = "HOXA9, MLL, MOZ, Symplekin, Transcription regulation",

author = "Anne Largeot and J{\'e}r{\^o}me Paggetti and Julien Bros{\'e}us and Romain Aucagne and Brice Lagrange and Martin, {Romain Z.} and Jean Berthelet and Ronan Qu{\'e}r{\'e} and G{\'e}raldine Lucchi and Patrick Ducoroy and Bastie, {Jean No{\"e}l} and Laurent Delva",

note = "Funding Information: This study was supported by grants from the Ligue contre le Cancer (Conf{\'e}rence de Coordination Inter-r{\'e}gionale du Grand Est) (to L.D.), the Conseil R{\'e}gional de Bourgogne (CRB) (PARI to RGHL team), and by a French Government grant managed by the French National Research Agency (ANR) under the program “ Investissements d'Avenir ” with reference ANR-11-LABX-0021 (LipSTIC Labex). A.L. was supported by fellowships from the Inserm associated with the CRB and the Soci{\'e}t{\'e} Fran{\c c}aise d'H{\'e}matologie (SFH) , J.P. by fellowships from the Minist{\`e}re de l'Enseignement Sup{\'e}rieur et de la Recherche of France (MESR) and the Association pour la Recherche sur le Cancer (ARC) , R.A. by fellowships from the Ligue de Sa{\^o}ne-et-Loire contre le Cancer , the ARC, and the SFH, B.L. by fellowships from the MESR, the ARC, and the SFH, R.Z.M. by fellowships from the MESR, R.Q. by fellowships from the CRB and the ARC, and J.Be. by the MESR. ",

year = "2013",

month = dec,

doi = "10.1016/j.bbamcr.2013.08.013",

language = "English",

volume = "1833",

pages = "3054--3063",

journal = "Biochimica et Biophysica Acta - Molecular Cell Research",

issn = "0167-4889",

publisher = "Elsevier B.V.",

number = "12",

}

Largeot, A , Paggetti, J, Broséus, J, Aucagne, R, Lagrange, B, Martin, RZ, Berthelet, J, Quéré, R, Lucchi, G, Ducoroy, P, Bastie, JN & Delva, L 2013, 'Symplekin, a polyadenylation factor, prevents MOZ and MLL activity on HOXA9 in hematopoietic cells', Biochimica et Biophysica Acta - Molecular Cell Research, vol. 1833, no. 12, pp. 3054-3063. https://doi.org/10.1016/j.bbamcr.2013.08.013

TY - JOUR

T1 - Symplekin, a polyadenylation factor, prevents MOZ and MLL activity on HOXA9 in hematopoietic cells

AU - Largeot, Anne

AU - Paggetti, Jérôme

AU - Broséus, Julien

AU - Aucagne, Romain

AU - Lagrange, Brice

AU - Martin, Romain Z.

AU - Berthelet, Jean

AU - Quéré, Ronan

AU - Lucchi, Géraldine

AU - Ducoroy, Patrick

AU - Bastie, Jean Noël

AU - Delva, Laurent

N1 - Funding Information: This study was supported by grants from the Ligue contre le Cancer (Conférence de Coordination Inter-régionale du Grand Est) (to L.D.), the Conseil Régional de Bourgogne (CRB) (PARI to RGHL team), and by a French Government grant managed by the French National Research Agency (ANR) under the program “ Investissements d'Avenir ” with reference ANR-11-LABX-0021 (LipSTIC Labex). A.L. was supported by fellowships from the Inserm associated with the CRB and the Société Française d'Hématologie (SFH) , J.P. by fellowships from the Ministère de l'Enseignement Supérieur et de la Recherche of France (MESR) and the Association pour la Recherche sur le Cancer (ARC) , R.A. by fellowships from the Ligue de Saône-et-Loire contre le Cancer , the ARC, and the SFH, B.L. by fellowships from the MESR, the ARC, and the SFH, R.Z.M. by fellowships from the MESR, R.Q. by fellowships from the CRB and the ARC, and J.Be. by the MESR.

PY - 2013/12

Y1 - 2013/12

N2 - MOZ and MLL encoding a histone acetyltransferase and a histone methyltransferase, respectively, are targets for recurrent chromosomal translocations found in acute myeloblastic or lymphoblastic leukemia. We have previously shown that MOZ and MLL cooperate to activate HOXA9 gene expression in hematopoietic stem/progenitors cells. To dissect the mechanism of action of this complex, we decided to identify new proteins interacting with MOZ. We found that the scaffold protein Symplekin that supports the assembly of polyadenylation machinery was identified by mass spectrometry. Symplekin interacts and co-localizes with both MOZ and MLL in immature hematopoietic cells. Its inhibition leads to a decrease of the HOXA9 protein level but not of Hoxa9 mRNA and to an over-recruitment of MOZ and MLL onto the HOXA9 promoter. Altogether, our results highlight the role of Symplekin in transcription repression involving a regulatory network between MOZ, MLL and Symplekin.

AB - MOZ and MLL encoding a histone acetyltransferase and a histone methyltransferase, respectively, are targets for recurrent chromosomal translocations found in acute myeloblastic or lymphoblastic leukemia. We have previously shown that MOZ and MLL cooperate to activate HOXA9 gene expression in hematopoietic stem/progenitors cells. To dissect the mechanism of action of this complex, we decided to identify new proteins interacting with MOZ. We found that the scaffold protein Symplekin that supports the assembly of polyadenylation machinery was identified by mass spectrometry. Symplekin interacts and co-localizes with both MOZ and MLL in immature hematopoietic cells. Its inhibition leads to a decrease of the HOXA9 protein level but not of Hoxa9 mRNA and to an over-recruitment of MOZ and MLL onto the HOXA9 promoter. Altogether, our results highlight the role of Symplekin in transcription repression involving a regulatory network between MOZ, MLL and Symplekin.

KW - HOXA9

KW - MLL

KW - MOZ

KW - Symplekin

KW - Transcription regulation

UR - http://www.scopus.com/inward/record.url?scp=84884334464&partnerID=8YFLogxK

U2 - 10.1016/j.bbamcr.2013.08.013

DO - 10.1016/j.bbamcr.2013.08.013

M3 - Article

AN - SCOPUS:84884334464

SN - 0167-4889

VL - 1833

SP - 3054

EP - 3063

JO - Biochimica et Biophysica Acta - Molecular Cell Research

JF - Biochimica et Biophysica Acta - Molecular Cell Research

IS - 12

ER -

Symplekin, a polyadenylation factor, prevents MOZ and MLL activity on HOXA9 in hematopoietic cells

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Keywords

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