Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the chicken lysozyme gene silencers binds two transcription factors, v-ERBA or the thyroid hormone receptor and NeP1 (negative protein 1), a new silencer binding protein. NeP1 is neutral on a monomeric binding site, but mediates weak repression on a multimerized site and strong synergistic repression in conjunction with v-ERBA on the wild-type silencer. Depending on the presence or absence of ligand, synergistic induction or repression is seen with the thyroid hormone receptor. This synergism is not based on cooperative DNA-binding as measured in vitro. The NeP1 DNA-binding activity is dependent on zinc ions, the binding site is characterized by a footprint of approximately 50 bp. NeP1 has a molecular weight of 140 to 160 kDa and has been enriched by affinity columns.
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PMID:NeP1. A ubiquitous transcription factor synergizes with v-ERBA in transcriptional silencing. 810 52

NeP1 binds to the F1 silencer element of the chicken lysozyme gene and, in the presence of TR, v-ERBA or RAR, synergistically represses transcriptional activity. This repression involves a silencing mechanism acting independently of the relative promoter position. Here we show that NeP1 alone can induce a significant directed bend on DNA. The chicken homologue of human NeP1, CTCF, shows identical binding and bending properties. In contrast, the isolated DNA binding domain of CTCF efficiently binds DNA, but fails to confer bending. Similarly, the TR-RXR hetero- or homodimer, binding adjacent to NeP1 at the F2 sequence, do not show significant DNA bending. The binding of the T3 ligand to TR changes neither the magnitude nor the direction of the NeP1 induced bend. However, when all factors are bound simultaneously as a quaternary complex, the TR-RXR heterodimer changes the location of the bend center, the flexure angle and the bending direction.
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PMID:DNA bending by the silencer protein NeP1 is modulated by TR and RXR. 875 89

The transcriptional repressor negative protein 1 (NeP1) binds specifically to the F1 element of the chicken lysozyme gene silencer and mediates synergistic repression by v-ERBA, thyroid hormone receptor, or retinoic acid receptor. Another protein, CCCTC-binding factor (CTCF), specifically binds to 50-bp-long sequences that contain repetitive CCCTC elements in the vicinity of vertebrate c-myc genes. Previously cloned chicken, mouse, and human CTCF cDNAs encode a highly conserved 11-Zn-finger protein. Here, NeP1 was purified and DNA bases critical for NeP1-F1 interaction were determined. NeP1 is found to bind a 50-bp stretch of nucleotides without any obvious sequence similarity to known CTCF binding sequences. Despite this remarkable difference, these two proteins are identical. They have the same molecular weight, and NeP1 contains peptide sequences which are identical to sequences in CTCF. Moreover, NeP1 and CTCF specifically recognize each other's binding DNA sequence and induce identical conformational alterations in the F1 DNA. Therefore, we propose to replace the name NeP1 with CTCF. To analyze the puzzling sequence divergence in CTCF binding sites, we studied the DNA binding of 12 CTCF deletions with serially truncated Zn fingers. While fingers 4 to 11 are indispensable for CTCF binding to the human c-myc P2 promoter site A, a completely different combination of fingers, namely, 1 to 8 or 5 to 11, was sufficient to bind the lysozyme silencer site F1. Thus, CTCF is a true multivalent factor with multiple repressive functions and multiple sequence specificities.
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PMID:Negative protein 1, which is required for function of the chicken lysozyme gene silencer in conjunction with hormone receptors, is identical to the multivalent zinc finger repressor CTCF. 903 55