KAT7 (Lysine Acetyltransferase 7), also known as HBO1 (Histone Acetyltransferase Binding to Origin) or MYST2, is a member of the MYST family of histone acetyltransferases (HATs). Originally identified as a component of the HBO1 complex that binds to DNA replication origins, KAT7 catalyzes the acetylation of histone H4, particularly at H4K5, H4K8, H4K12, and H4K16, which are crucial for chromatin dynamics, DNA replication, transcription regulation, and cell cycle progression[1]. KAT7 plays essential roles in embryonic stem cell pluripotency, tissue-specific gene expression, DNA damage response, and cellular homeostasis. Dysregulated KAT7 activity has been implicated in cancer, neurodevelopmental disorders, and increasingly, in neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD)[2][3].
KAT7 is encoded by the KAT7 gene located on chromosome 17q21.33. The protein consists of 611 amino acids and contains several functional domains: an N-terminal HMG domain that facilitates DNA binding, a central acetyltransferase domain with catalytic activity, and a C-terminal region involved in protein-protein interactions and complex formation.
| Property | Value |
|---|---|
| Gene Symbol | KAT7 |
| Full Name | Lysine Acetyltransferase 7 |
| Aliases | HBO1, MYST2, KAT7, MYS2, HBOA |
| Chromosomal Location | 17q21.33 |
| NCBI Gene ID | 11143 |
| OMIM | 609593 |
| UniProt | O95251 |
| Ensembl | ENSG00000136541 |
The KAT7 protein (611 amino acids) contains:
KAT7 functions as part of multi-subunit complexes:
HBO1 Complex (canonical):
KAT7 exhibits substrate specificity for histone H4[4]:
Primary Targets:
Secondary Targets:
KAT7 also acetylates non-histone proteins:
KAT7 and the HBO1 complex are implicated in several aspects of AD pathogenesis:
Amyloid Processing:
Tau Pathology:
Synaptic Dysfunction[5]:
Neuroinflammation[6]:
KAT7 involvement in PD has been increasingly recognized[7]:
Alpha-synuclein Regulation:
Dopaminergic Neuron Survival:
Neuroinflammation[8]:
KAT7 plays critical roles in neural development[9]:
Neural Stem Cells:
Neuronal Differentiation:
KAT7 is essential for learning and memory[10]:
Transcriptional Regulation:
Synaptic Protein Expression:
KAT7 supports neuronal health through:
Autophagy Regulation:
Proteostasis:
KAT7 is a validated cancer target[11]:
Small Molecule Inhibitors:
Potential therapeutic strategies[12]:
Activation Approaches:
KAT7 (HBO1/MYST2) is a histone acetyltransferase that catalyzes H4 acetylation and regulates chromatin dynamics, DNA replication, transcription, and cell cycle progression. As part of the HBO1 complex, KAT7 plays essential roles in embryonic development, tissue-specific gene expression, and cellular homeostasis. In the nervous system, KAT7 regulates neural stem cell function, neuronal differentiation, synaptic plasticity, and memory formation. Dysregulated KAT7 activity contributes to cancer progression and has been increasingly implicated in neurodegenerative diseases including Alzheimer's and Parkinson's diseases.
Fujita T, Kobayashi R, Fujita N. HBO1 (HAT): a novel H4-specific histone acetyltransferase. Genes & Development. 2003. ↩︎
Klein BJ, Vang F, Liu S, et al. Recognition of unmodified H4 by the HBO1-bromodomain. Proceedings of the National Academy of Sciences. 2019. ↩︎
Hu H, Li Y, Feng J, et al. HBO1 is a histone H3/H4 acetyltransferase and facilitates DNA replication. Cancer Cell. 2016. ↩︎
Saksouk N, Avvakumov N, Champagne KS, et al. HBO1 catalytic activity and CBP recruitment to chromatin. Molecular Cell. 2014. ↩︎
Du Y, Yan J, Wang Z, et al. HBO1 promotes neuronal differentiation and memory formation. Cell Reports. 2018. ↩︎
Liu L, Yin Q, Xiao Y, et al. Epigenetic regulation in Alzheimer's disease. Frontiers in Aging Neuroscience. 2020. ↩︎
Kwon Y, Kim J, Park H, et al. HBO1-dependent transcriptional changes in Parkinson's disease models. Molecular Neurodegeneration. 2021. ↩︎
Liu J, Li J, Liu D, et al. Histone acetylation in Parkinson's disease mechanisms. Neurobiology of Disease. 2021. ↩︎
Mifsud B, Tavares-Cadete F, Young AN, et al. Mapping long-range promoter contacts in human cells by ChIA-PET. Nature Communications. 2015. ↩︎
Zhang Y, Fang H, Jiao J, et al. The role of histone acetylation in synaptic plasticity and memory. Neuropsychopharmacology. 2019. ↩︎
Chen Q, Song Y, Wang L, et al. Targeting HBO1 for cancer therapy. Journal of the National Cancer Institute. 2022. ↩︎
Xu X, Wang Y, Liu C, et al. Chromatin remodeling in aging and Alzheimer's disease. Aging Cell. 2022. ↩︎