Ten-Eleven Translocation 2 (TET2) is a pivotal α-ketoglutarate and Fe2+-dependent dioxygenase belonging to the TET family, governing epigenetic homeostasis through DNA, RNA, and histone modifications. Its central function involves the iterative oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further derivatives, initiating active DNA demethylation. Beyond this, TET2 catalyzes RNA m5C oxidation and interacts with histone modifiers, thus modulating diverse cellular processes. Physiologically, TET2 is indispensable for hematopoietic stem cell (HSC) function, genomic stability, and the resolution of inflammation. Its dysregulation, often driven by somatic mutations, is implicated across a broad spectrum of human diseases. These include hematological malignancies, solid tumors, inflammatory disorders, cardiovascular diseases (CVD), metabolic abnormalities, and neurological conditions. Notably, TET2 exhibits strong context dependency, functioning as a tumor suppressor in myeloid malignancies while exerting distinct immunomodulatory roles in certain solid tumors. This review systematically summarizes recent advances in the molecular mechanisms and physiological functions of TET2, and highlights its disease-specific roles and promising therapeutic strategies. We also discuss unresolved challenges and future research directions to facilitate the clinical translation of TET2-related epigenetic findings.
Jingyi Tang, Ruoxian Wang, Li Long et al.· Frontiers in Immunology· 0 citations
Meprin and TRAF-C homology (MATH) proteins function as adaptor molecules and components of E3 ubiquitin ligase complexes. They link receptor-like kinase signalling to downstream regulatory pathways in plants. MATH proteins coordinate growth, hormone signalling, and responses to abiotic stress by modulating ubiquitin-dependent proteostasis. Despite their importance, however, little is known about the diversity, function, and specific regulatory role of the
MATH
gene family in
Brassica napus
.
We identified 151
BnMATH
family genes distributed across the 19 chromosomes of
B. napus
using a hidden Markov model-based genome-wide search followed by domain validation. Comparative phylogenetic and structural analyses classified these genes into four conserved clades, revealing that extensive segmental and tandem duplication events had driven the family expansion. Promoter analysis revealed more than 6,000 cis-acting regulatory elements associated with hormone- and stress-responsive gene expression. A total of 44 miRNA families targeting BnMATH genes were identified, among which 10 have been previously validated to be involved in biological processes. Transcriptome profiling combined with qRT-PCR validation revealed pronounced tissue-specific and abiotic-stress-responsive expression patterns. Notably,
BnMATH06
,
BnMATH92,
and
BnMATH135
were strongly induced by salt and drought stress, suggesting a potential role in stress adaptation.
These findings deepen our understanding of the
MATH
gene family and provide a robust foundation for future functional genomics research targeting their specific biological roles, particularly in hormone-driven regulation and adaptation to abiotic stress.
Fatima Maliha, Wenyu Wu, Li Long et al.· BMC Plant Biology· 0 citations
