B lymphocytes are generated from hematopoietic stem cells, a process controlled by multiple transcription factors (i.e. PU.1, E2A etc.). In addition, concerted changes of chromatin structure at the target gene loci are required to achieve desired developmental outcomes. It is known that a compact chromatin state would prevent transcription factors from DNA-binding and gene expression initiation while a loose structure favors binding. However, the process by which chromatin remodeling affects B cell lymphopoiesis has not been fully understood. I am currently studying a novel B cell deficient mouse model in which B cell development is severely impaired due to a point mutation in a putative chromatin remodeling protein.
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Lu P, Hankel IL, Hostager BS, Swartzendruber JA, Friedman AD, Brenton JL, Rothman PB, Colgan JD. The developmental regulator protein Gon4l associates with protein YY1, co-repressor Sin3a, and histone deacetylase 1 and mediates transcriptional repression. J Biol Chem. 2011 May 20;286(20):18311-9. Epub 2011 Mar 29. PubMed PMID: 21454521; PubMed Central PMCID: PMC3093903.
Lu P, Hankel IL, Knisz J, Marquardt A, Chiang MY, Grosse J, Constien R, Meyer T, Schroeder A, Zeitlmann L, Al-Alem U, Friedman AD, Elliott EI, Meyerholz DK, Waldschmidt TJ, Rothman PB, Colgan JD. The Justy mutation identifies Gon4-like as a gene that is essential for B lymphopoiesis. J Exp Med. 2010 Jul 5;207(7):1359-67. Epub 2010 Jun 7. PubMed PMID: 20530203; PubMed Central PMCID: PMC2901076.
Kashiwada M, Lu P, Rothman PB. PIP3 pathway in regulatory T cells and autoimmunity. Immunol Res. 2007;39(1-3):194-224. Review. PubMed PMID: 17917066.