Page last updated: 2024-10-24

negative regulation of core promoter binding

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of core promoter binding. [GO_REF:0000059, GOC:BHF, GOC:BHF_telomere, GOC:nc, GOC:TermGenie, PMID:22723415]

Negative regulation of core promoter binding is a complex process that involves the suppression of transcription initiation by inhibiting the binding of transcription factors to the core promoter region of a gene. The core promoter is a DNA sequence located upstream of the transcription start site that serves as a platform for the assembly of the transcription pre-initiation complex (PIC). This complex comprises RNA polymerase II, general transcription factors (GTFs), and other regulatory proteins that are essential for initiating transcription.

The negative regulation of core promoter binding can occur through various mechanisms, including:

**1. Competitive Inhibition:**
- Repressor proteins can compete with activator proteins for binding to the core promoter. This competition prevents the assembly of the PIC and inhibits transcription initiation.

**2. Blocking of Transcription Factor Binding Sites:**
- Repressor proteins can bind to specific DNA sequences within the core promoter that overlap with the binding sites of activator proteins. This physically blocks the activator proteins from binding and prevents the assembly of the PIC.

**3. Recruitment of Corepressor Proteins:**
- Repressor proteins can recruit corepressor proteins that directly interact with the PIC, preventing its assembly or function. Corepressors can modify histones to make the chromatin less accessible to the transcriptional machinery, or they can directly inhibit the activity of GTFs.

**4. Modification of the Core Promoter Structure:**
- Some repressor proteins can alter the structure of the core promoter DNA, making it less conducive to the binding of activator proteins or the assembly of the PIC.

**5. Interference with Chromatin Remodeling:**
- Repressor proteins can influence the accessibility of the core promoter by affecting chromatin remodeling processes. For instance, they can recruit histone deacetylases (HDACs) that remove acetyl groups from histones, leading to a more condensed chromatin state that inhibits transcription.

In summary, negative regulation of core promoter binding is a multifaceted process involving the suppression of transcription initiation by interfering with the binding of transcription factors to the core promoter. This regulation can occur through various mechanisms, including competitive inhibition, blocking of binding sites, recruitment of corepressors, modification of promoter structure, and interference with chromatin remodeling.'
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Proteins (1)

ProteinDefinitionTaxonomy
Presenilin-1A presenilin-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P49768]Homo sapiens (human)

Compounds (22)

CompoundDefinitionClassesRoles
tocopheroxy radicaltocopheroxy radical: RN given refers to radical ion (1+), (2R-(2R*(4R*,8R*)))-isomer; RN for cpd without isomeric designation not available 12/90tocopherol
7-amino-4-chloro-3-methoxy-2-benzopyran-1-oneisocoumarins
tarenflurbiltarenflurbil: R-enantiomer of flurbiprofen but not a COX inhibitor; modulates NF-kB, gamma-secretase, amyloid beta-protein;flurbiprofen
cholanic acid5beta-cholanic acids;
cholanic acid
t0901317T0901317: an LXRalpha and LXRbeta agonist
n-(n-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl esterDAPT : A dipeptide consisting of alanylphenylglycine derivatised as a 3,5-difluorophenylacetamide at the amino terminal and a tert-butyl ester at the carboxy terminal. A gamma-secretase inhibitor.carboxylic ester;
difluorobenzene;
dipeptide;
tert-butyl ester
EC 3.4.23.46 (memapsin 2) inhibitor
sulindac sulfidesulindac sulfide : An aryl sulfide that is a metabolite of sulindac. A non-steroidal anti-inflammatory drug, which also has anticancer activity.

sulindac sulfide: sulfated analog of indomethacin & inhibitor of prostaglandin synthesis in vitro; RN given refers to cpd without isomeric designation; structure given in first source
aryl sulfide;
monocarboxylic acid;
organofluorine compound
antineoplastic agent;
apoptosis inducer;
non-steroidal anti-inflammatory drug
l 685458L 685458: a gamma-secretase inhibitor; structure in first source

L-685,458 : A peptide and carboxamide that is L-leucyl-L-phenylalaninamide, L-Leu-L-Phe-NH2, which has been acylated on the N-terminus by a Phe-Phe hydroxyethylene dipeptide isotere, 2R-benzyl-5S-tert-butoxycarbonylamino-4R-hydroxy-6-phenylhexanoic acid. Compounds based on the structure of L-685,458 are potent inhibitors of gamma-secretase, which mediates the final catalytic step that generates the amyloid beta-peptide (Abeta), which assembles into the neurotoxic aggregates in the brains of sufferers of Alzheimer's disease.
carbamate ester;
monocarboxylic acid amide;
peptide;
secondary alcohol
EC 3.4.23.46 (memapsin 2) inhibitor;
peptidomimetic
mk 0752
ly 450139peptide
chf 50741-(3',4'-dichloro-2-fluoro(1,1'-biphenyl)-4-yl)cyclopropanecarboxylic acid: a beta-amyloid(1-42) lowering agent; structure in first source
ly 411575dibenzoazepine;
difluorobenzene;
lactam;
secondary alcohol
EC 3.4.23.46 (memapsin 2) inhibitor
4-(2-((1r)-1-(((4-chlorophenyl)sulfonyl)-2,5-difluoroanilino)ethyl)-5-fluorophenyl)butanoic acidsulfonamide
begacestat
e 2012
mrk 560MRK 560: a gamma-secretase inhibitor; MRK-560 is the (cis)-isomer; structure in first source
1, 3-di-(n-carboxybenzoyl-leucyl-leucyl)amino acetone1, 3-di-(N-carboxybenzoyl-leucyl-leucyl)amino acetone: structure in first source
pf 3084014nirogacestat : A member of the class of imidazoles that is 1H-imidazole substituted by a 1-[(2,2-dimethylpropyl)amino]-2-methylpropan-2-yl group at position 1 and a {N-[(2S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]-L-norvalyl}amino group at position 4. It is a gamma-secretase inhibitor whose hydrobromide salt is indicated for adult patients with progressing desmoid tumours who require systemic treatment.

nirogacestat: an antineoplastic agent
bms 708163BMS 708163: structure in first sourceoxadiazole;
ring assembly
ro 4929097dibenzoazepine;
dicarboxylic acid diamide;
lactam;
organofluorine compound
EC 3.4.23.46 (memapsin 2) inhibitor
jnj 40418677
(r)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1h-pyrazolo(4,3-c)quinoline(R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo(4,3-c)quinoline: gamma secretase inhibitor; structure in first source