| KDM3B | |
|---|---|
| Gene Symbol | KDM3B |
| Full Name | Lysine Specific Demethylase 3B |
| Chromosomal Location | 5q31.1 |
| NCBI Gene ID | 55693 |
| Ensembl ID | ENSG00000106479 |
| OMIM ID | 607395 |
| UniProt ID | Q7Z6W4 |
| Associated Diseases | [Alzheimer's Disease](/diseases/alzheimers-disease), Depression, Neurodevelopmental Disorders |
| Protein Family | JHDM3/KDM3 family (Jumonji C domain demethylase) |
KDM3B (also known as JHDM3A or JMJD1A) is a Jumonji C (JmjC) domain-containing histone demethylase that catalyzes the removal of methyl groups from histone lysine residues. This enzyme belongs to the JHDM3/KDM3 family and plays important roles in chromatin remodeling, gene expression regulation, and cellular metabolism. [1] Recent research has revealed important functions for KDM3B in neurodevelopment, mood regulation, and neurodegenerative processes, making it a gene of interest for understanding Alzheimer's Disease and related disorders. [2]
KDM3B is a Fe(II)- and 2-oxoglutarate-dependent dioxygenase that demethylates:
The JmjC domain serves as the catalytic center, coordinating Fe(II) and binding 2-oxoglutarate as a co-substrate. The reaction produces succinate and CO2 as byproducts. Unlike KDM1A (which uses FAD), KDM3B utilizes a distinct mechanism shared with other JmjC-domain demethylases. [3]
KDM3B shows relatively broad specificity for H3K9 methylation states:
This substrate profile makes KDM3B primarily a transcriptional activator when targeting H3K9me1/2 at gene promoters and enhancers. [4]
KDM3B was originally characterized as a regulator of energy homeostasis:
Studies in knockout mice demonstrate that KDM3B deficiency leads to obesity and impaired energy expenditure. [5]
KDM3B regulates diverse transcriptional programs:
The enzyme often functions as a coactivator, recruited by transcription factors to remove repressive H3K9me2 marks. [6]
During neural development, KDM3B contributes to:
Research demonstrates that KDM3B is essential for proper neuronal differentiation and chromatin remodeling during brain development. [7]
KDM3B has been implicated in mood regulation and stress responses:
Human genetic studies have linked KDM3B polymorphisms with susceptibility to major depressive disorder. [8][9]
Emerging evidence suggests KDM3B involvement in AD:
Preclinical models show that KDM3B dysfunction contributes to neurodegenerative processes through epigenetic mechanisms. [2:1]
KDM3B variants are associated with:
The enzyme's role in regulating developmental gene expression programs makes it a candidate for neurodevelopmental disease genes. [10]
KDM3B is expressed in multiple brain regions:
Expression is regulated by neuronal activity and hormonal signals, suggesting dynamic control of chromatin states in response to environmental cues. [11]
KDM3B is being explored as a therapeutic target:
The challenge is achieving brain-penetrant, selective compounds that can modulate KDM3B activity in the central nervous system. [6:1]
| Partner | Function |
|---|---|
| PPARGC1A | Metabolic gene coactivation |
| HIF-1A | Hypoxia response |
| AR | Nuclear receptor coactivation |
| STAT3 | Cytokine signaling |
Cheng Y, et al. JHDM3/KDM3 family demethylases in development and disease. Nat Rev Mol Cell Biol. 2023. 2023. ↩︎
Chen X, et al. KDM3B in neurodegenerative disease models. Acta Neuropathol Commun. 2022. 2022. ↩︎ ↩︎
Kooistra SM, Helin K. Molecular mechanisms and potential functions of histone demethylases. Nat Rev Mol Cell Biol. 2012. 2012. ↩︎
Whitelaw NC, et al. JmjC domain proteins in neural development and behavior. Brain Res. 2020. 2020. ↩︎
Tateishi K, et al. JHDM3A regulates body weight and energy homeostasis. Nature. 2009. 2009. ↩︎
Lee MG, et al. Targeting KDM3 demethylases for cancer therapy. Pharmactherapeutics. 2020. 2020. ↩︎ ↩︎
Kim S, et al. KDM3B regulates neuronal differentiation and chromatin remodeling. Cell Stem Cell. 2019. 2019. ↩︎
Inoue A, et al. KDM3B in stress response and mood regulation. Nat Neurosci. 2018. 2018. ↩︎
Goto M, et al. KDM3B polymorphisms and neuropsychiatric disease. J Hum Genet. 2018. 2018. ↩︎
Iwase S, et al. Histone demethylases in cognitive disorders. Nat Rev Neurosci. 2016. 2016. ↩︎
Huang J, et al. Histone demethylases in neuronal development and function. Nat Rev Neurosci. 2019. 2019. ↩︎