KAT7 — Lysine Acetyltransferase 7 (HBO1/MYST2)

KAT7 — Lysine Acetyltransferase 7 (HBO1/MYST2)

Overview

KAT7 — Lysine Acetyltransferase 7 (HBO1/MYST2)

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">KAT7 — Lysine Acetyltransferase 7 (HBO1/MYST2)</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>KAT7</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Lysine Acetyltransferase 7</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>HBO1, MYST2, KAT7, MYS2, HBOA</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>17q21.33</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>11143</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>609593</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>O95251</td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td>ENSG00000136541</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
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<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">12 edges</a></td>
</tr>
</table>

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

Gene Information

Protein Domains

The KAT7 protein (611 amino acids) contains:

Complex 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

• 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

• H4ac at tau gene promoters
• Modulates tau expression levels

• Impaired H4ac at synaptic gene promoters
• Memory consolidation defects

• 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

• Protection against oxidative stress

• 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

• 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

• 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

• 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

Pathway Diagram

The following diagram shows the key molecular relationships involving KAT7 — Lysine Acetyltransferase 7 (HBO1/MYST2) discovered through SciDEX knowledge graph analysis: