Biomaterial Database

Modulation of thyroid hormone receptor silencing function by co-repressors and a synergizing transcription factor. 2000

M Lutz, and A Baniahmad, and R Renkawitz

Genetisches Institut, Justus-Liebig-Universität, D-35392 Giessen, Germany.

We have found that the thyroid hormone receptor (T3R) functionally synergizes with the CCCTC-binding factor (CTCF). CTCF is a highly conserved zinc-finger protein that has been connected with multiple functions in gene regulation including chromatin insulator activity, transcriptional enhancement and silencing as well as tumour suppression. A specific property of CTCF is that some of the binding sites are found in the vicinity of T3R-binding sites. Interestingly, both factors synergize in repression as well as in activation. T3R-mediated repression has been shown to involve co-repressors such as the silencing mediator for retinoic acid and thyroid hormone receptor (SMRT), N-CoR or Alien. These co-repressors in turn have been found to interact with Sin3A. Until now, the mechanisms by which CTCF synergizes with T3R in transcriptional repression has not been determined. Here we show that CTCF comprises autonomous silencing domains that mediate transcriptional repression when tethered to a promoter sequence. At least one of these domains, the zinc-finger region of CTCF, binds Sin3A without binding to SMRT or N-CoR and recruits histone deacetylation activity. For Sin3A we identified two different domains interacting independently with the CTCF zinc-finger cluster. The ability of regions of CTCF to retain deacetylase activity is correlated with the ability to bind to Sin3A and to repress transcription. Taking these results together, the synergy in repression mediated by T3R and CTCF might be achieved by the binding of multiple molecules of Sin3A to the T3R/CTCF-DNA complex, thus providing a large platform for the recruitment of histone deacetylases.

UI	MeSH Term	Description	Entries
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009687	Nuclear Proteins	Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.	Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D011401	Promoter Regions, Genetic	DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.	rRNA Promoter,Early Promoters, Genetic,Late Promoters, Genetic,Middle Promoters, Genetic,Promoter Regions,Promoter, Genetic,Promotor Regions,Promotor, Genetic,Pseudopromoter, Genetic,Early Promoter, Genetic,Genetic Late Promoter,Genetic Middle Promoters,Genetic Promoter,Genetic Promoter Region,Genetic Promoter Regions,Genetic Promoters,Genetic Promotor,Genetic Promotors,Genetic Pseudopromoter,Genetic Pseudopromoters,Late Promoter, Genetic,Middle Promoter, Genetic,Promoter Region,Promoter Region, Genetic,Promoter, Genetic Early,Promoter, rRNA,Promoters, Genetic,Promoters, Genetic Middle,Promoters, rRNA,Promotor Region,Promotors, Genetic,Pseudopromoters, Genetic,Region, Genetic Promoter,Region, Promoter,Region, Promotor,Regions, Genetic Promoter,Regions, Promoter,Regions, Promotor,rRNA Promoters
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011988	Receptors, Thyroid Hormone	Specific high affinity binding proteins for THYROID HORMONES in target cells. They are usually found in the nucleus and regulate DNA transcription. These receptors are activated by hormones that leads to transcription, cell differentiation, and growth suppression. Thyroid hormone receptors are encoded by two genes (GENES, ERBA): erbA-alpha and erbA-beta for alpha and beta thyroid hormone receptors, respectively.	Diiodotyrosine Receptors,Receptors, Diiodotyrosine,Receptors, Thyroxine,Receptors, Triiodothyronine,T3 Receptors,T4 Receptors,Thyroid Hormone Receptors,Thyroxine Receptors,Triiodothyronine Receptors,DIT Receptors,Diiodotyrosine Receptor,MIT Receptors,Monoiodotyrosine Receptors,Receptors, DIT,Receptors, MIT,Receptors, Monoiodotyrosine,Receptors, T3,Receptors, T4,T3 Receptor,T4 Receptor,Thyroid Hormone Receptor,Thyroxine Receptor
D012097	Repressor Proteins	Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.	Repressor Molecules,Transcriptional Silencing Factors,Proteins, Repressor,Silencing Factors, Transcriptional
D002843	Chromatin	The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.	Chromatins
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004268	DNA-Binding Proteins	Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.	DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D004641	Emigration and Immigration	The process of leaving one's country to establish residence in a foreign country.	Immigration,Labor Migration,Border Crossing,Chain Migration,Emigration,In-Migration,International Migration,Out-Migration,Return Migration,Settlement and Resettlement,Temporary Migration,Turnaround Migration,Border Crossings,Chain Migrations,Crossing, Border,Crossings, Border,Emigrations,Immigration and Emigration,Immigrations,In Migration,In-Migrations,International Migrations,Labor Migrations,Migration, Chain,Migration, International,Migration, Labor,Migration, Return,Migration, Temporary,Migration, Turnaround,Migrations, Chain,Migrations, International,Migrations, Labor,Migrations, Return,Migrations, Temporary,Migrations, Turnaround,Out Migration,Out-Migrations,Resettlement and Settlement,Return Migrations,Temporary Migrations,Turnaround Migrations