A human B-cell interactome identifies MYB and FOXM1 as master regulators of proliferation in germinal centers.
Assembly of a transcriptional and post-translational molecular interaction network in B cells, the human B-cell interactome (HBCI), reveals a hierarchical, transcriptional control module, where MYB and FOXM1 act as synergistic master regulators of proliferation in the germinal center (GC). Eighty percent of genes jointly regulated by these transcription factors are activated in the GC, including those encoding proteins in a complex regulating DNA pre-replication, replication, and mitosis. These results indicate that the HBCI analysis can be used for the identification of determinants of major human cell phenotypes and provides a paradigm of general applicability to normal and pathologic tissues.
Lefebvre
Celine
C
Center for Computational Biology and Bioinformatics, Columbia University, New York, NY 10032, USA.
Rajbhandari
Presha
P
Alvarez
Mariano J
MJ
Bandaru
Pradeep
P
Lim
Wei Keat
WK
Sato
Mai
M
Wang
Kai
K
Sumazin
Pavel
P
Kustagi
Manjunath
M
Bisikirska
Brygida C
BC
Basso
Katia
K
Beltrao
Pedro
P
Krogan
Nevan
N
Gautier
Jean
J
Dalla-Favera
Riccardo
R
Califano
Andrea
A
D000465:Algorithms; D017209:Apoptosis / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D004261:DNA Replication / Q000235:genetics; D025461:Feedback, Physiological; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D005809:Genes, Regulator / Q000235:genetics*; D018858:Germinal Center / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008938:Mitosis; D046912:Multiprotein Complexes / Q000378:metabolism; D011485:Protein Binding; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D014158:Transcription, Genetic
C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D046912:Multiprotein Complexes; D020598:Proto-Oncogene Proteins c-myb