This information is current as Growth of Developing and Mature T Cells BTB-ZF Protein Znf 131 Regulates Cell

Many members of the BTB-ZF family have been shown to play important roles in lymphocyte development and function. The role of zinc finger Znf131 (also known as Zbtb35) in T cell lineage was elucidated through the production of mice with floxed allele to disrupt at different stages of development. In this article, we present that Znf131 is critical for T cell development during double-negative to double-positive stage, with which significant cell expansion triggered by the pre-TCR signal is coupled. In mature T cells, Znf131 is required for the activation of effector genes, as well as robust proliferation induced upon TCR signal. One of the cyclin-dependent kinase inhibitors, p21 Cip1 encoded by cdkn1a gene, is one of the targets of Znf131. The regulation of T cell proliferation by Znf131 is in part attributed to its suppression on the expression of p21 Cip1. T he broad complex, tramtrack, bric a brac and zinc finger (BTB-ZF) family comprises .60 members of transcription factors (1–3). Many members have been shown to play important roles in the development and function of lymphocytes. Many of the BTB-ZF proteins recruit various corepressors and other epigenetic regulators to suppress transcription. Developmental steps in thymus can be subdivided into four functional stages. The first step is to establish T lineage commitment, which requires various signals including Notch activation. Induction and maintenance of core transcription factors required for T lineage specification and simultaneous turning off of non–T cell lineage differentiation are coordinately regulated by stimuli from the thymic environment (4, 5). The second step designated as b-selection and/or gd-selection is to select cells that productively rearrange either TCRb locus or TCRg and d loci. Stimulation signal emanating from pre-TCR, TCRb-chain associated with the invariant surrogate a-chain, pTa, in addition to Notch signal is required for differentiation into CD4 + CD8 + double-positive (DP) stage accompanied by profound cell proliferation. Miz1 (Zbtb17), a member of the BTB-ZF family, drives DP differentiation by counteracting p53-dependent pathway (6). The third step is to eliminate self-reactive clones (negative selection) and nonreactive cells while selecting out clones receiving moderate TCR signal (positive selection) and to generate other types of T cells such as thymic regulatory T cells and invariant NK T cells (7, 8). Moreover, branching into CD4 single-positive (SP) Th cell precursors or into CD8 SP cytotoxic T cell precursors takes place. Another BTB-ZF family transcription factor ThPOK (Zbtb7b) is a major regulator for …