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)

Osteocalcin (OC) is a bone-specific protein which is expressed postproliferatively by osteoblasts during late stages of differentiation. We have found that a silencer element is present within the rat OC gene (between nt +39 and +104), overlapping the OC signal prepropeptide-coding sequence. The presence of this sequence in OC promoter-CAT reporter constructs suppresses promoter activity in transiently transfected proliferating osteoblasts, which do not express OC, by up to 50-fold. This is the first demonstration of contribution from protein-coding sequences to silencing of animal genes. The element appears to be bipartite; silencer activity requires both the protein-coding sequence +39 to +63 and the +93 to +104 exon 1/intron 1 border region. Both of these domains contain sequences highly similar to silencer motifs in several other genes, including chicken lysozyme as well as rat collagen type II, insulin, and growth hormone. OC silencer activity is fully retained when the element is placed outside the RNA-coding region, 3' but not 5' of the OC-CAT fusion gene. Repression activity is orientation independent in the native position but requires the native orientation when located in 3' extragenic positions. The silencer does not inhibit the activity of the heterologous SV40 early promoter. These results suggest interaction between the transcribed silencer and specific OC promoter element(s) residing farther upstream. The OC transcribed silencer may contribute to developmental control of OC expression.
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PMID:Position and orientation-selective silencer in protein-coding sequences of the rat osteocalcin gene. 750 55

The chicken lysozyme locus is regulated in oviduct and macrophages by a complex set of well-characterized cis-regulatory DNA elements. We determined the DNase I hypersensitive chromatin site pattern of the chromatin of the lysozyme locus in retrovirally transformed cell lines representing different stages of myelomonocytic cell differentiation. In the transformed multipotent progenitor stage and in erythroblasts, only a DNase I hypersensitive chromatin site at a silencer element located -2.4 kb upstream of the transcriptional start site is present. At the myeloblast stage DNase I hypersensitive chromatin sites are formed both at the distal enhancer located at -6.1 kb and at the promoter. Later in differentiation, at the monocytic stage, a second DNase I hypersensitive chromatin site appears at the medial enhancer located at -2.7 kb. Parallel with DNase I hypersensitive chromatin site formation at the medial enhancer, the DNase I hypersensitive chromatin site at the silencer element disappears. These chromatin rearrangements correlate with the mRNA expression of the gene that is undetectable in multipotent progenitors and maximal in a lipopolysaccharide-stimulated monocyte cell line. Our results show that the chromatin structure and the transcriptional activity of the gene are tightly coupled during commitment and maturation of the myelomonocytic lineage.
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PMID:Dynamic changes in the chromatin of the chicken lysozyme gene domain during differentiation of multipotent progenitors to macrophages. 774 89

Thyroid hormone receptors (TRs) bind specific thyroid hormone response elements (TREs) as heterodimers with retinoid X receptors (RXRs) and act as transcriptional activators. As homodimers, TRs can bind a distinct set of sequences and function as ligand sensitive repressors. In our study, we compared the natural malic enzyme TRE (ME-TRE) as a model system for the TR/RXR heterodimer pathway to the chicken lysozyme silencer element F2-TRE which is strongly bound and regulated by TR/TR homodimers. Using electrophoretic mobility shift assays, transient transfections with a variety of natural and synthetic triiodothyronine and thyroxine derivatives as well as limited proteolytic analysis, we show that the natural homo- and heterodimeric pathways show similar ligand requirements. Furthermore, we observe that the ligand-induced conformational changes in the receptor proteins that either result in a loss of TR/TR homodimer binding and release of transcriptional repression or in transcriptional activation of TR/RXR heterodimers are indistinguishable. Therefore, we propose that in TR/TR homodimers and TR/RXR heterodimers very similar moieties of the receptors are involved in ligand binding and subsequent conformational changes that lead to loss of gene repression (TR/TR homodimer) and gain of gene activation (TR/RXR heterodimer).
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PMID:Similar ligand-induced conformational changes of thyroid hormone receptors regulate homo- and heterodimeric functions. 785 92

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