mechanism 833 words KG: ent-gene-caf074c2 2026-03-29
kind:section:mechanismsevidence:strongmechanismsection:mechanismsstate:publishedmechanism-type:transcriptional-dysregulationdisease:huntingtons-disease
Contents

HTT Transcriptional Dysregulation Pathway

🔬 Protein Info
Gene Symbolent-gene-caf074c2
FunctionCBP is a histone acetyltransferase (HAT) and transcriptional coactivator
Normal functionWild-type huntingtin sequesters REST in the cytoplasm, preventing REST from entering the nucleus
In HDMutant huntingtin loses this function, allowing REST to translocate to the nucleus
ConsequenceReduced histone acetylation and transcriptional silencing[@mcquaid2016]
Target genesN-methyl-D-aspartate (NMDA) receptor subunits, synapsins, neurotrophic peptides
InteractionmHTT binds to Sp1 and TAFII130 (TBP-associated factor)
Affected pathwaysDNA repair genes, anti-apoptotic proteins
Nuclear accumulationmHTT promotes p53 nuclear accumulation
Transcriptional shiftp53 shifts from pro-survival to pro-apoptotic gene targets
SequestrationmHTT aggregates trap CBP, reducing its nuclear availability
Therapeutic targetHDAC inhibitors can partially restore CBP function
KG Connections2 knowledge graph edges
DatabasesGeneCardsUniProtNCBI GeneHPASTRING

Knowledge Graph

Related Hypotheses (29)

Trinucleotide Repeat Sequestration via CRISPR-Guided RNA Tar
Score: 0.48
Bacterial Enzyme-Mediated Dopamine Precursor Synthesis
Score: 0.36
Acid-Degradable LNP-Mediated Prenatal CRISPR Intervention fo
Score: 0.47
Hippocampal CA3-CA1 circuit rescue via neurogenesis and syna
Score: 0.68
Vagal Afferent Microbial Signal Modulation
Score: 0.52

Related Analyses (30)

CRISPR-based therapeutic approaches for neurodegenerative di
neurodegeneration · completed
CRISPR-based therapeutic approaches for neurodegenerative di
neurodegeneration · archived
Astrocyte reactivity subtypes in neurodegeneration
neurodegeneration · archived
Blood-brain barrier transport mechanisms for antibody therap
neurodegeneration · archived
Autophagy-lysosome pathway convergence across neurodegenerat
neurodegeneration · archived

Related Experiments (7)

s:** - Temporal analysis showing mitochondrial defects prece
falsification · proposed · Score: 0.40
Epigenetic Dysregulation in Huntington's Disease — Therapeut
validation · proposed · Score: 0.40
Mutant Huntingtin (mHTT) Clearance Mechanisms — Therapeutic
validation · proposed · Score: 0.40
Alpha-Synuclein Aggregation Triggers — Sporadic PD Initiatio
clinical · proposed · Score: 0.40
tACS Connectivity Trial in Early Alzheimer's
clinical · proposed · Score: 0.40

Knowledge Graph (2 edges)

ent-gene-caf074c2 data_in benchmark_ot_ad_answer_key:HTT
benchmark_ot_ad_answer_key:HTT data_in ent-gene-caf074c2