William J. Romanow
University of California, San Diego
GeneRecombination-activating geneMolecular biologyT-cell receptorBiology
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Publications 6
#1Shuji Sakamoto (Kyoto University)H-Index: 3
#2Kousho Wakae (Kyoto University)H-Index: 2
Last. Yasutoshi AgataH-Index: 18
view all 14 authors...
V(D)J recombination of Ig and TCR genes is strictly regulated in a lineage- and stage-specific manner by the accessibility of target gene chromatin to the recombinases RAG1 and RAG2. It has been shown that enforced expression of the basic helix–loop–helix protein, E2A, together with RAG1/2 in a nonlymphoid cell line BOSC23 can induce V(D)J recombination in endogenous Igκ and TCR loci by increasing chromatin accessibility of target gene segments. In this study, we demonstrate that ectopically exp...
22 CitationsSource
#1Melanie W. QuongH-Index: 9
#2William J. RomanowH-Index: 6
Last. Cornelis MurreH-Index: 65
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Lymphocytes arise from hematopoietic stem cells through the coordinated action of transcription factors. The E proteins (E12, E47, HEB and E2-2) have emerged as key regulators of both B and T lymphocyte differentiation. This review summarizes the current data and examines the various functions of E proteins and their antagonists, Id2 and Id3, throughout lymphoid maturation. Beyond an established role in B and T lineage commitment, E proteins continue to be essential at subsequent stages of devel...
174 CitationsSource
#1Peter GoebelH-Index: 4
#2Noel JanneyH-Index: 1
Last. Ann J. FeeneyH-Index: 34
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Accessibility of immunoglobulin (Ig) gene segments to V(D)J recombination is highly regulated and is normally only achieved in B cell precursors. We previously showed that ectopic expression of E2A or early B cell factor (EBF) with recombination activating gene (RAG) induces rearrangement of IgH and IgL genes in nonlymphoid cells. VκI genes throughout the locus were induced to rearrange after transfection with E2A, suggesting that the entire Vκ locus was accessible. However, here we show that Ig...
102 CitationsSource
During specific stages of thymocyte development, the T cell receptor (TCR) locus is assembled from variable (V), diversity (D), and joining (J) gene segments. Proper TCR γ and δ V(D)J rearrangement during thymocyte development requires the presence of the E2A proteins. Here we show that E2A and a closely related protein, HEB, in the presence of recombination activating gene (RAG)1 and RAG2, each have the ability to activate TCR γ and δ rearrangement in human kidney cells. The coding joints are d...
37 CitationsSource
#1William J. Romanow (UCSD: University of California, San Diego)H-Index: 6
#2Anton W. Langerak (EUR: Erasmus University Rotterdam)H-Index: 54
Last. Cornelis Murre (UCSD: University of California, San Diego)H-Index: 65
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Abstract Immunoglobulin (Ig) and T cell receptor (TCR) genes are assembled during lymphocyte maturation through site-specific V(D)J recombination events. Here we show that E2A proteins act in concert with RAG1 and RAG2 to activate Ig Vκ1J but not Igλ VλIII–Jλ1 rearrangement in an embryonic kidney cell line. In contrast, EBF, but not E2A, promotes VλIII–Jλ1 recombination. Either E2A or EBF activate IgH D H 4J recombination but not V(D)J rearrangement. The Ig coding joints are diverse, contain nuc...
213 CitationsSource
A key feature of B and T lymphocyte development is the generation of antigen receptors through the rearrangement and assembly of the germline variable (V), diversity (D), and joining (J) gene segments. However, the mechanisms responsible for regulating developmentally ordered gene rearrangements are largely unknown. Here we show that the E2A gene products are essential for the proper coordinated temporal regulation of V(D)J rearrangements within the T cell receptor (TCR) γ and δ loci. Specifical...
106 CitationsSource