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Identification of an essential site for transcriptional activation within the human T-cell receptor. delta. enhancer

Journal Article · · Molecular and Cellular Biology; (United States)
; ;  [1]
  1. Duke Univ., Durham, NC (United States)
A T-cell-specific transcriptional enhancer was previously identified within the J{sub {delta}3}-C{sub {delta}} intron of the human T-cell receptor (TCR) {delta} gene, and seven distinct binding sites for nuclear factors ({delta}E1 to {delta}E7) were defined by DNase I footprinting. In this study, conducted a detailed functional analysis of the various cis-acting DNA sequence elements of the enhancer and show that a 60-bp fragment encompassing {delta}E3 and {delta}E4 displays potent enhancer activity, as judged by its ability to activate transcription from the V{sub {delta}}1 promoter. They show that the interaction of nuclear factors with the {delta}E3 site is essential for enhancer activity. This element displays significant activity in the absence of additional segments of the enhancer. Further, methylation interference and in vitro mutagenesis identify a site within {delta}E3 that mediates the binding of two nuclear factors (NF-{delta}E3A and NF-{delta}E3C) and that is required for significant transcriptional activation by the enhancer. NF-{delta}E3C is ubiquitous and may be identical to a previously characterized {mu}E3-binding factor, NF-{delta}E3A is preferentially expressed in T lymphocytes, and the authors suggest that this factor may play the dominant role in transcriptional activation through the {delta}E3 site. One of three specific complexes formed with a {delta}E4 probe appears to be T-cell specific.
OSTI ID:
5116419
Journal Information:
Molecular and Cellular Biology; (United States), Journal Name: Molecular and Cellular Biology; (United States) Vol. 11:11; ISSN MCEBD; ISSN 0270-7306
Country of Publication:
United States
Language:
English