Regulation of B cell transcription and development Lymphocyte differentiation proceeds through multiple stages characterized by the expression of distinct sets of genes. My laboratory’s goals include understanding how the nuclear proteins Early B cell Factor (EBF) and Pax5 (B cell-specific activator protein) regulate B lineage specification, commitment and the immune response to antigens. EBF has been identified as a crucial factor for lineage determination. EBF regulates many genes (such as mb-1) involved in assembly of the pre-B and mature B cell receptors for antigen (pre-BCR and BCR). We recently identified EBF as an early mediator of changes in mb-1 gene chromatin structure, including DNA demethylation and enhanced accessibility. Pax5 acts downstream of EBF as an important regulator of the early B cell-specific transcriptome, but is also important at later stages of B cell maturation. Notably, Pax5 is a key factor for establishing B cell lineage commitment. To better understand how these proteins function in B cells, my lab employs a combination of biochemical and genetic methods, including transgenic and gene targeted mice. Ultimately, we wish to understand how regulatory signals are integrated for activation and/or repression of genes that contribute to normal immunity, immune diseases, and cancer.
Lukin, K, S Fields, L Guerrettaz, D Straign, V Rodriguez, S Zandi, R Månsson, JC Cambier, M Sigvardsson and J Hagman. 2011. A dose-dependent role for EBF1 in repressing non-B cell specific genes. Eur J Immunol, 41:1787-1793 (PMCID: PMC3127254).
Musselman, CA, J Ramirez, JK Sims, RE Mansfield, SS Oliver, JM Denu, JP Mackay, PA Wade, J Hagman and TG Kutateladze. 2012. Bivalent recognition of nucleosomes by the tandem PHD fingers of CHD4 is required for CHD4-mediated repression. Proc Natl Acad Sci USA, 109:787-792 (PMCID: PMC3271909).
Hagman, J, J Ramírez and K Lukin. 2012. B lymphocyte lineage specification, commitment and epigenetic control of transcription by Early B cell Factor 1. Curr Topics Micro Immunol, 356:17-38 (PMID: 21735360).
Dege, C, and J Hagman. 2012. Activation of Aicda gene transcription by Pax5 in plasmacytoma cells. Immunol Res, [Epub ahead of print] (PMID: 22956488).
Ramirez, J, C Dege, KG Kutateladze and J Hagman. 2012. MBD2 and multiple domains of CHD4 are required for transcriptional repression by Mi-2/NuRD complexes. Mol Cell Biol, [Epub ahead of print] (PMID: 23071088).