Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The IgH enhancer is a strong lymphoid-specific activator and is composed of multiple factor-binding motifs. One of these, the octamer, is common to enhancer and promoter, binds ubiquitous and lymphoid-specific factors and is able to act as a lymphoid-specific transcriptional activator. However, it is also found as an essential component of promoters active in non-lymphoid cells. From analysis of the activities of synthetic promoters, we suggest that recruitment of the lymphoid-specific octamer-binding protein next to the TATA is sufficient to create a functional lymphoid-specific promoter whereas the ubiquitous octamer binding protein is not active in single copy but can act in concert with other promoter binding factors. However, the activity of the IgH enhancer is not dependent on the octamer and we identify the E2/E3 elements as also being sufficient to confer lymphoid-specificity on a linked gene. Activity of the E2/E3 region results from the synergistic activity of the two motifs, E2 alone being able to confer a low level of activity which is dramatically increased by the adjacent E3. Thus, in the case of both the E2/E3 and the octamer motifs, interactions between adjacent elements can play a critical role in determining the tissue specificity of activity.
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PMID:Lymphoid-specific transcriptional activation by components of the IgH enhancer: studies on the E2/E3 and octanucleotide elements. 211 13

MyoD is a muscle-specific transcriptional activator; E12 is a B-cell activator. An IgH enhancer is activated almost 100-fold by E12 but not at all by Myo; an MCK enhancer is activated almost 1000-fold by MyoD and not at all by E12. MyoD and E12 are both basic helix-loop-helix proteins that bind to similar E-box sequences (CANNTG); the IgH enhancer contains the same E boxes as the MCK enhancer, yet each retains exclusive specificity for either E12 or MyoD, respectively. We show that the IgH enhancer contains a cis-acting negative element that is directed at MyoD, but not at E12. This repression requires the mu E5 E box within the IgH enhancer; however, the specificity for repression, as opposed to activation, is associated with 2 bp flanking each side of the mu E5 E box. The target for repression of MyoD in the IgH enhancer is the bHLH region of MyoD. Our results suggest that MyoD only activates myogenic genes because nonmuscle enhancers that contain E boxes also contain negative elements that prevent MyoD activity.
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PMID:Tissue-specific gene activation by MyoD: determination of specificity by cis-acting repression elements. 795 89

Proliferation and differentiation of B lymphocytes are usually concurrent but independently regulated events. Anti-mu treatment of murine B lymphocytes stimulated with LPS provides a model system in which proliferation and differentiation may be independently studied. This treatment causes enhanced proliferation but with coordinate suppression of transcription of a family of unrelated genes including those for Ig heavy and light chains, J chain, and endogenous murine leukemia virus (MuLV) sequences. We show that in comparison to B lymphocytes stimulated with LPS alone cells stimulated with a combination of anti-mu and LPS exhibit relatively increased amounts of a nuclear binding factor(s), NF mu E1, which interacts with the B (mu E1) site of the IgH enhancer; binding is strongly inhibited by a synthetic probe of the B sequence. A negative regulatory sequence contained within the upstream conserved region (UCR) of the MuLV long terminal repeat (LTR) is identical to the complement of mu E1 in eight of nine bases and inhibits binding of NF mu E1 to the IgH enhancer probe. The mu E1 site is also present 3' to the kappa-light chain gene; binding of this sequence to a repressor protein may coordinately suppress the transcription of mu, kappa, and MuLV genes. Others have reported that the cDNA encoding NF mu E1, also known as mu EBP-B, CF-1, and YY-1, predicts a protein with structural features consistent with variable function as either a transcriptional activator or repressor.
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PMID:Coordinate transcriptional control of murine endogenous retrovirus and Ig genes during B cell differentiation. 839 53

The mouse 3' enhancer contains a high-affinity binding site for the paired box protein Pax-5. Here, we demonstrate by genomic footprinting that the rat 3' enhancer contains a low-affinity binding site for Pax-5, which is occupied in activated splenic B cells. Thus, binding of Pax-5 to the IgH 3' enhancer appears to be evolutionarily conserved in rodents. Analysis of Pax-5 expression in primary B cells demonstrates that Pax-5 remains expressed after 4 days of lipopolysaccharide (LPS) induction, but is down-regulated in 5-day stimulated cells. Similarly, the expression of Pax-5 is down-regulated in vivo in activated large splenocytes, in contrast to small resting cells. Multimerization of the high-affinity Pax-5 binding site linked to a heterologous reporter gene demonstrates that Pax-5 can function as a transcriptional activator. In contrast, Pax-5 overexpressed in cell lines represses both the mouse and the rat 3' enhancer. Surprinsingly, cross-linking of the IgM receptor in BAL-17 cells containing a stably integrated 3' enhancer-dependent beta globin reporter gene demonstrates that induction of 3' enhancer activity is not blocked by Pax-5. Moreover, stimulation of 3' enhancer beta globin-transgenic splenocytes demonstrate that Pax-5 cannot repress-activation of the 3' enhancer upon LPS induction or CD40 receptor stimulation. Hence, activation of the IgH 3' enhancer occurs independently of changes in Pax-5 gene expression. This indicates that previous studies conducted in vitro may be an oversimplification of the function of Pax-5 and 3' enhancer activity.
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PMID:Physiological activation of the IgH 3' enhancer in B lineage cells is not blocked by Pax-5. 889 66

Bright (B cell regulator of IgH transcription) is a B cell-specific, matrix associating region-binding protein that transactivates gene expression from the IgH intronic enhancer (E mu). We show here that Bright has multiple contextual requirements to function as a transcriptional activator. Bright cannot transactivate via out of context, concatenated binding sites. Transactivation is maximal on integrated substrates. Two of the three previously identified binding sites in E mu are required for full Bright transactivation. The Bright DNA binding domain defined a new family, which includes SWI1, a component of the SWI.SNF complex shown to have high mobility group-like DNA binding characteristics. Similar to one group of high mobility group box proteins, Bright distorts E mu binding site-containing DNA on binding, supporting the concept that it mediates E mu remodeling. Transfection studies further implicate Bright in facilitating spatially separated promoter-enhancer interactions in both transient and stable assays. Finally, we show that overexpression of Bright leads to enhanced DNase I sensitivity of the endogenous E mu matrix associating regions. These data further suggest that Bright may contribute to increased gene expression by remodeling the immunoglobulin locus during B cell development.
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PMID:Transcriptional activation by a matrix associating region-binding protein. contextual requirements for the function of bright. 1129 36