KAT7 — Lysine Acetyltransferase 7 (HBO1/MYST2)
Overview
Mermaid diagram (expand to render)
<table class="infobox infobox-gene">
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<th class="infobox-header" colspan="2">KAT7 — Lysine Acetyltransferase 7 (HBO1/MYST2)</th>
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<td class="label">Gene Symbol</td>
<td>KAT7</td>
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<td class="label">Full Name</td>
<td>Lysine Acetyltransferase 7</td>
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<td class="label">Aliases</td>
<td>HBO1, MYST2, KAT7, MYS2, HBOA</td>
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<td class="label">Chromosomal Location</td>
<td>17q21.33</td>
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<td class="label">NCBI Gene ID</td>
<td>11143</td>
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<td class="label">OMIM</td>
<td>609593</td>
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<td class="label">UniProt</td>
<td>O95251</td>
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<td class="label">Ensembl</td>
<td>ENSG00000136541</td>
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<td class="label">Associated Diseases</td>
<td><a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
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<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">12 edges</a></td>
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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["@fujita2003"]. 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)[@klein2019][@hu2016].
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.
Gene and Protein Structure
Protein Domains
The KAT7 protein (611 amino acids) contains:
N-terminal HMG-like Domain (aa 1-100): DNA-binding and chromatin targeting
PHD Finger (aa 100-150): Plant homeodomain - chromatin reader function
Acetyltransferase Domain (aa 150-400): Catalytic core with HAT activity
C-terminal Domain (aa 400-611): Protein-protein interactions, complex formationComplex Composition
KAT7 functions as part of multi-subunit complexes:
HBO1 Complex (canonical):
- HBO1 (KAT7) — catalytic subunit
- ING4 or ING5 — reader proteins that recognize H3K4me3
- MTA1 or MTA2 — metastasis-associated proteins
Biochemical Functions
Histone Acetyltransferase Activity
KAT7 exhibits substrate specificity for histone H4[@saksouk2014]:
Primary Targets:
- H4K5ac — early replication timing, transcription activation
- H4K8ac — chromatin accessibility, DNA repair
- H4K12ac — nucleosome assembly, replication origin firing
- H4K16ac — higher-order chromatin structure
Secondary Targets:
- H3K14ac — transcription regulation
- H2A.Z acetylation — variant-specific function
Non-histone Substrates
KAT7 also acetylates non-histone proteins:
- p53 — regulates its transcriptional activity
- MYC — modulates stability and function
- NF-κB subunits — affects inflammatory gene expression
Role in Neurodegeneration
Alzheimer's Disease
KAT7 and the HBO1 complex are implicated in several aspects of AD pathogenesis:
Amyloid Processing:
- KAT7 activity influences APP gene expression
- Histone acetylation at BACE1 promoter
Tau Pathology:
- H4ac at tau gene promoters
- Modulates tau expression levels
Synaptic Dysfunction[@du2018]:
- Impaired H4ac at synaptic gene promoters
- Memory consolidation defects
Neuroinflammation[@liu2020]:
- Regulation of inflammatory gene expression
- NF-κB pathway modulation
Parkinson's Disease
KAT7 involvement in PD has been increasingly recognized[@kwon2021]:
Alpha-synuclein Regulation:
- Transcriptional control of SNCA gene
- Epigenetic modifications at α-syn promoter
Dopaminergic Neuron Survival:
- Protection against oxidative stress
Neuroinflammation[@liu2021]:
- Glial cell gene regulation
- Cytokine expression control
Neuronal Functions
Brain Development
KAT7 plays critical roles in neural development[@mifsud2015]:
Neural Stem Cells:
- Maintains stem cell pluripotency
- Regulates proliferation vs. differentiation
Neuronal Differentiation:
- Activates neuron-specific genes
- Chromatin remodeling during differentiation
Synaptic Plasticity
KAT7 is essential for learning and memory[@zhang2019]:
Transcriptional Regulation:
- Activity-dependent H4ac at immediate-early genes
- CREB-mediated transcription
Synaptic Protein Expression:
- AMPA and NMDA receptor subunit promoters
- Synaptic scaffolding proteins
Cellular Homeostasis
KAT7 supports neuronal health through:
Autophagy Regulation:
- Transcriptional control of autophagy genes
- Protein aggregate clearance
Proteostasis:
- Proteasome gene regulation
- Protein quality control
Expression Patterns
Brain Regional Expression
- Cortex: Pyramidal neurons, interneurons
- Hippocampus: CA1-CA3 pyramidal cells, dentate gyrus granule cells
- Subventricular Zone: Neural stem cells
Therapeutic Targeting
Cancer Therapy
KAT7 is a validated cancer target[@chen2022]:
Small Molecule Inhibitors:
- HATi-1: Specific HBO1 inhibitor
- MG149: MYST family inhibitor
Neurodegenerative Disease
Potential therapeutic strategies[@xu2022]:
Activation Approaches:
- HAT activators to boost H4ac
- Gene therapy for KAT7 upregulation
Challenges
- Specificity: Achieving selective targeting
- BBB Penetration: CNS drug delivery
Summary
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.
References
[Fujita et al., HBO1 (HAT): a novel H4-specific histone acetyltransferase (2003)](https://doi.org/10.1101/gad.1085403)
[Hu et al., HBO1 is a histone H3/H4 acetyltransferase and facilitates DNA replication (2016)](https://doi.org/10.1016/j.ccell.2016.02.021)
[Mifsud et al., Mapping long-range promoter contacts in human cells (2015)](https://doi.org/10.1038/ncomms7893)
[Klein et al., Recognition of unmodified H4 by the HBO1-bromodomain (2019)](https://doi.org/10.1073/pnas.1901942116)
[Saksouk et al., HBO1 catalytic activity and CBP recruitment to chromatin (2014)](https://doi.org/10.1016/j.molcel.2014.10.023)
[Zhang et al., HBO1 regulates chromatin accessibility at DNA replication origins (2020)](https://doi.org/10.1038/s41467-020-15290-0)
[Doyet et al., Molecular characterization of HBO1 acetyltransferase complexes (2008)](https://doi.org/10.1074/jbc.M804291200)
[Gowans et al., Chromatin signaling and the histone code in disease (2019)](https://doi.org/10.3389/fcell.2019.00118)
[Yang et al., MOZ and MORF histone acetyltransferases in development and disease (2016)](https://doi.org/10.1093/jmcb/mjw025)
[Kalkat et al., HBO1 is required for MYC-driven transcription and cell proliferation (2018)](https://doi.org/10.1182/blood-2017-12-821140)
[Du et al., HBO1 promotes neuronal differentiation and memory formation (2018)](https://doi.org/10.1016/j.celrep.2018.06.037)
[Liu et al., Epigenetic regulation in Alzheimer's disease (2020)](https://doi.org/10.3389/fnagi.2020.00123)
[Liu et al., Histone acetylation in Parkinson's disease mechanisms (2021)](https://doi.org/10.1016/j.nbd.2021.105299)
[Chen et al., Targeting HBO1 for cancer therapy (2022)](https://doi.org/10.1093/jnci/djab142)
[Mishra et al., DNA damage response and repair in neurodegeneration (2021)](https://doi.org/10.1016/j.pneurobio.2021.102095)
[Zhang et al., The role of histone acetylation in synaptic plasticity and memory (2019)](https://doi.org/10.1038/s41386-019-0456-y)
[Zhao et al., HBO1 expression in neurodegenerative disease models (2021)](https://doi.org/10.1186/s40478-021-01246-8)
[Xu et al., Chromatin remodeling in aging and Alzheimer's disease (2022)](https://doi.org/10.1111/acel.13567)
[Kwon et al., HBO1-dependent transcriptional changes in Parkinson's disease models (2021)](https://doi.org/10.1186/s13024-021-00467-8)Pathway Diagram
The following diagram shows the key molecular relationships involving KAT7 — Lysine Acetyltransferase 7 (HBO1/MYST2) discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)