Search Results (1,644)

The methylation of CpG sites with 5mC mark is a dynamic epigenetic modification. However, the relationship between the methylation and the surrounding genomic sequence context remains poorly explored. Investigation of the allele methylation provides an opportunity to decipher the interplay between differences in the primary DNA sequence and epigenetic variation. Here, we performed high-coverage long-read whole-genome direct DNA sequencing of one individual using Oxford Nanopore technology. We also used Illumina whole-genome sequencing of the parental genomes in order to identify allele-specific methylation sites with a trio-binning approach. We have compared the results of the haplotype-specific methylation detection and revealed that trio binning outperformed other approaches that do not take into account parental information. Also, we analysed the cis-regulatory effects of the genomic variations for influence on CpG methylation. To this end, we have used available Deep Learning models trained on the primary DNA sequence to score the cis-regulatory potential of the genomic loci. We evaluated the functional role of the allele-specific epigenetic changes with respect to gene expression using long-read Nanopore RNA sequencing. Our analysis revealed that the frequency of SNVs near allele-specific methylation positions is approximately four times higher compared to the biallelic methylation positions. In addition, we identified that allele-specific methylation sites are more conserved and enriched at the chromatin states corresponding to bivalent promoters and enhancers. Together, these findings suggest that significant impact on methylation can be encoded in the DNA sequence context. In order to elucidate the effect of the SNVs around sites of allele-specific methylation, we applied the Deep Learning model for detection of the cis-regulatory modules and estimated the impact that a genomic variant brings with respect to changes to the regulatory activity of a DNA loci. We revealed higher cis-regulatory impact variants near differentially methylated sites that we further coupled with transcriptomic long-read sequencing results. Our investigation also highlights technical aspects of allele methylation analysis and the impact of sequencing coverage on the accuracy of genomic phasing. In particular, increasing coverage above 30X does not lead to a significant improvement in allele-specific methylation discovery, and only the addition of trio binning information significantly improves phasing. We investigated genomic variation in a single human individual and coupled computational discovery of cis-regulatory modules with allele-specific methylation (ASM) profiling. In this proof-of-concept analysis, we observed that SNPs located near methylated CpG sites on the same haplotype were enriched for sequence features suggestive of high-impact regulatory potential. This finding—derived from one deeply sequenced genome—illustrates how phased genetic and epigenetic data analyses can jointly put forward a hypotheses about the involvement of regulatory protein machinery in shaping allele-specific epigenetic states. Our investigation provides a methodological framework and candidate loci for future studies of genomic imprinting and cis-mediated epigenetic regulation in humans. Full article

Background/Objectives: Prenatal exposure to famine can lead to lasting health effects through changes in DNA methylation. This study aims to evaluate the impact of prenatal exposure to the Chinses Great Famine (1959–1961) on human epigenome and the subsequent influence on blood lipids. Methods: We conducted an epigenome-wide association study (EWAS) of peripheral blood-based DNA methylation and prenatal exposure to the Chinese Great Famine as well as blood lipids among eight participants exposed to famine and eight sex-matched participants (born ≤ 3 years after the famine). Genome-wide DNA methylation sites were profiled using the Illumina EPIC BeadChip, which covers 850K methylation positions. Results: After EWAS analyses, seven probes in genes C8orf31, ELAVL1, U6, GBA2, SHOX2, SLC1A4, and NPHP4 reached p < 1 × 10⁻⁵. Of these, famine exposure was associated with decreased methylation levels of a GBA2 exonic probe cg08258661 (p = 4.9 × 10⁻⁶). After false discovery rate (FDR) correction, pathway enrichment analyses for genes harboring nominally significant (p < 0.05) probes identified 44 significant pathways (q < 0.05), and 5 pathways were related to lipid metabolism. After FDR correction in each pathway, probes cg02622866 (5’UTR of ATF2, p = 1.09 × 10⁻³), cg07316730 (body of GRB2, p = 1.32 × 10⁻³), and cg01105385 (body of PIK3R1, p = 1.94 × 10⁻³) in the PI2K-Akt signaling pathway were associated with blood LDL-C (q ≤ 0.04); probes cg09180702 (3’UTR of PIGQ, p = 9.21 × 10⁻⁵, and q = 0.04) and cg01421548 (body of HS3ST4, p = 5.23 × 10⁻⁵, and q = 0.01) in the metabolism pathway were associated with blood LDL-C and HDL-C, respectively; In addition, probe cg08460387 (5’UTR of MAN1C1, p = 1.09 × 10⁻⁴, and q = 0.02) in the vesicle-mediated transport pathway was associated with log-transformed blood triglycerides. Conclusions: Through an epigenetic study of the Chinese Great Famine, we identified six novel genes involved in lipid metabolism. Full article

(1) Background: Pigs can be another host of Shiga toxin-producing E. coli (STEC), suggesting that pork products could be a potential risk to public health. A USDA National Animal Health Monitoring System (NAHMS) study revealed that Shiga toxin genes were detected in more than half of samples nationwide but only about a quarter of samples from the state of Illinois. To characterize the presence of STEC in Illinois pigs better and to explore the discrepancy between Illinois and other swine-producing states, we increased the sampling size and collected samples in different regions of the state and in different months to detect Shiga toxin genes in Illinois finisher pigs and subtyped the Shiga toxin genes further to assess any potential risk of STEC originating from Illinois pigs to human health. (2) Methods: Fecal samples were collected from 471 Illinois finisher pigs at different locations from October 2021 to September 2022. DNA samples were extracted from individual fecal samples and PCR-tested for Shiga toxin genes (stx1, stx2) and then toxin subtypes (stx2a, stx2c, stx2d, and stx2e). (3) Results: The data showed that the stx2 gene was detected in 61% of the fecal samples (285/471), whereas stx1 was detected only in 0.4% of the samples (2/471). The data also indicated a lower prevalence of stx genes in the samples collected in certain cold months (36% in October and 19% in March) compared to that in those from warm months (56% to 100% from April to September). Stx2d, a subtype associated with severe human illness, was detected in 2% of the samples (10/471); in contrast, stx2e, which is expressed by E. coli strains causing diarrhea and edema disease in pigs, was the most detected (49%; 229/471). (4) Conclusions: The high prevalence of Shiga toxin genes in the fecal samples from Illinois finisher pigs suggests that Stx-positive E. coli strains circulate in Illinois pig farms. However, the highly detected stx2e-positive STEC (or enterotoxigenic E. coli, ETEC) strains are associated with diarrhea and edema disease in pigs, indicating the need for disease prevention or control for pigs but unlikely a safety concern for Illinois pork products or a major risk of human illnesses. Full article

Cellular organisms store heritable information in two forms, genetic and epigenetic, the latter being largely dependent on cytosine methylation (5mC). Chargaff’s Second Parity Rule (CSPR) describes the nucleotide composition of cellular genomes in terms of intra-strand DNA symmetry. However, it remains unknown whether DNA methylation patterns display intra-strand DNA symmetry. Computational analysis was conducted of the DNA methylation patterns observed in human cell lines and in tissue samples from healthy donors. Analysis of 5mC marks in mutually reverse-complementary pairs of short oligomers, containing CpG dinucleotide in the middle, revealed deviations from CSPR and methylation asymmetry that can be observed for two non-overlapping mirror groups defined by CpG methylation values. Deviations from CSPR, together with combinatorial probabilities of pattern distributions and computer simulations, highlight the non-random nature of methylation processes and enabled us to identify specific cell types as outliers. Further analysis revealed a compensatory methylation asymmetry that reduces deviations from intra-strand symmetry and implies the existence of strand-specific methylation during cell differentiation. Among six pairs of reverse-complementary tetranucleotides, four pairs with specific sequence motifs display pronounced methylation asymmetry. This mirror asymmetry may be associated with chromosome folding and the formation of a complex three-dimensional landscape. Full article

Background: Oncogenic fusions of MAML2 with CRTC1, CRTC3, YAP1, and NR1D1 retain the MAML2 transactivating domain (TAD) and are believed to drive aberrant gene transcription. While the oncogenic roles of these known fusions have been established, we aimed to identify novel MAML2 fusions across a range of human malignancies. Methods: DNA and RNA sequencing were performed on tumor samples submitted to Caris Life Sciences. MAML2 fusions were identified from RNA transcripts and filtered to include only known pathogenic fusions or recurrent, in-frame fusions containing a C-terminal MAML2 TAD. Fusion burden was defined as the number of unique fusion isoforms per sample. Results: Among 180,124 tumor samples, 143 specimens harbored MAML2 fusions with a MAML2 TAD: >50% of specimens harbored known fusions, but novel fusions with MTMR2 (31/143), SESN3 (11/143), CCDC82 (6/143), FAM76B (4/143), and ATXN3 (3/143) were also identified. Compared to the known fusions, the novel fusions generally had lower expressions (median: 8 vs. 13 junction reads/sample, p = 0.0064), higher fusion burdens (median: 6 vs. 2 unique fusion isoforms/sample, p < 0.0001), more frequent TP53 co-mutations (80% vs. 11.5%, p < 0.0001), and no clear association with the tissue of origin. Excluding ATXN3::MAML2, the novel fusion partners were located near MAML2 in the genome, likely arose from duplications or deletions, and occurred in samples harboring concurrent mutations. In contrast, ATXN3::MAML2 arose via interchromosomal translocation, occurred in samples with a low fusion burden, and was not associated with TP53 mutations. Conclusions: We identified novel MAML2 fusion partners, most of which likely represent passenger alterations, possibly arising from genomic instability or impaired p53 function. However, ATXN3::MAML2 fusions, previously reported in a pre-cancerous pancreatic disease case, may represent a pathogenic alteration warranting further investigation. Full article

Gossypol, a polyphenolic naphthalene derivative and yellow polyphenolic pigment found in cotton seed glands, presents notable environmental, animal, and human health hazards. To screen for yeast strains capable of utilizing gossypol and to investigate their removal efficiency and mechanisms. Yeast strains capable of utilizing gossypol as the exclusive carbon source were isolated from cotton field soil. The identification of these strains involved assessment of colony morphology, physiological and biochemical characteristics, and phylogenetic analysis utilizing 26S rDNA gene sequences. Safety evaluations included hemolytic and antibiotic susceptibility tests. The growth responses of the selected strains to varying temperatures and pH levels were determined. Using cotton meal as the solid fermentation substrate, the effects of single factors on gossypol removal by the strains were determined. The intracellular and extracellular localization as well as the nature of the gossypol-removing active components in the strains were characterized, followed by an investigation into the molecular mechanism of gossypol removal using LC-MS analysis. A total of 17 gossypol-utilizing strains were isolated from cotton field soil samples, with strain ZYS-3 demonstrating superior removal capability. Strain ZYS-3 was identified as Meyerozyma guilliermondii, exhibiting no hemolytic activity and susceptibility to nine commonly used antifungal agents. The optimal growth parameters for this strain were determined to be a temperature of 30 °C and a pH of 5.0. In solid-state fermentation using cotton meal at 30 °C with initial fermentation conditions (10% corn flour added as an external carbon source, 40% moisture content, and 6% inoculum concentration) for 3 days, strain ZYS-3 achieved a gossypol removal rate of 73.57%. Subsequent optimization of the fermentation process, including the addition of 10% corn flour as an external carbon source, adjustment of moisture content to 55%, and inoculum concentration to 10%, resulted in an increased gossypol removal rate of 89.77% after 3 days of fermentation, representing a 16.2% enhancement over the initial conditions. Assessment of gossypol removal activity revealed that strain ZYS-3 predominantly removes gossypol through the secretion of extracellular enzymes targeting specific active groups (phenolic hydroxyl groups and aldehyde groups) within the gossypol molecule. These enzymes facilitate oxidation and elimination reactions, leading to the opening of the naphthalene ring and subsequent removal of gossypol. Full article

Background/Objectives: Intrinsically disordered protein regions (IDRs) are difficult to study due to their flexible nature and transient interactions. Computational folding using AlphaFold may offer one way to explore potential folding of these regions under various conditions. Human DNA topoisomerase IIα (TOP2A) is an essential enzyme involved in regulating DNA topology during replication and cell division. TOP2A has an IDR at the C-terminal domain (CTD) that has been shown to be important for regulating TOP2A function, but little is known about potential conformations that it may undertake. Methods: Utilizing the AlphaFold 3 (AF3) model by way of AlphaFold Server, TOP2A was folded as a dimer first without and then with 29 literature-supported post-translational modifications (PTMs) and DNA to observe whether there is predicted folding. Results: TOP2A CTD does not fold in the absence of PTMs. With the addition of PTMs, however, the CTD is predicted to fold into a globular bundle of loops and α-helices. While DNA alone did not induce folding, in the presence of PTMs, DNA ligands increased helicity of the folded CTD and caused it to interact at different core domain interfaces. In addition, DNA is predicted to enable folding of the TOP2A CTD in the presence of fewer PTMs when compared to the absence of DNA. Conclusions: AF3 predicts the folding of TOP2A CTD in the presence of specific PTMs, and this folding appears to shift to allow binding to DNA in functionally relevant regions. These studies provide predicted folding patterns that can be tested by biochemical approaches. AF3 may support the development of testable hypotheses regarding IDRs and enables researchers to model protein-DNA interactions. Full article

Beyond sensing bitter-tasting compounds, bitter taste receptors (TAS2Rs) have been demonstrated to play a functional role in proton secretion as a key mechanism of gastric acid secretion (GAS) and the cellular uptake of the zinc metal ion. Given its chemical similarity and comparable effects in GAS, we focused this work on cadmium and hypothesized that gastric TAS2Rs are involved in (i) cadmium-induced inhibition of proton secretion and (ii) in its cellular uptake. To test this hypothesis, immortalized human parietal HGT-1 cells were exposed to 62.5–1000 µM CdCl₂ for 30 min to elucidate TAS2R-mediated proton secretory activity (PSA) using a fluorescence-based pH cell assay and to quantitate cellular cadmium uptake by ICP-MS. HGT-1 cells exposed to CdCl₂ exhibited a dose-dependent decrease in PSA, accompanied by a corresponding increase in intracellular cadmium concentrations. Following a TAS2R RT-qPCR screening, the functional roles of TAS2R8 and TAS2R10 were clarified using a siRNA knockdown approach, demonstrating that TAS2R8 promotes and TAS2R10 mediates protection against excessive cellular cadmium accumulation. An additional cDNA microarray screening revealed, via gene ontology analysis, a distinct gene association of TAS2R8 and TAS2R10 with several metal ion transporters. These results provide the first evidence for a specific role of individual TAS2Rs beyond taste perception, particularly in metal ion homeostasis and gastric physiology. Full article

Chlorella species are classified as functional food, with great anticancer effects. Despite the huge popularity of Chlorella-based products, there is a lack of evidence showing their usefulness in the prevention and treatment of endometrial cancer. The study presented here aimed to enrich knowledge resources in this area. The chemopreventive effect of water extracts of Chlorella pyrenoidosa was investigated in human endometrial adenocarcinoma HEC-1-B, KLE and EDC cells using MTT, BrdU, LDH, Wound assays, Cell Death Detection ELISA and nuclear double staining. C. pyrenoidosa extract inhibited the metabolic activity, DNA synthesis and migratory capacity of endometrial cancer cells. Moreover, the extract eliminated cancer cells, causing damage to their cell membranes and inducing apoptosis. The cells most resistant to chlorella extract were EDC cells (low grade), while the best response to the treatment was noted in KLE cells (high grade). The performed study revealed the chemopreventive properties of C. pyrenoidosa extract based on inhibition of endometrial cancer cell viability, proliferation and migratory capacity, as well as induction of cytotoxicity and apoptosis. Collected data suggested enhancement of extract chemopreventive properties with increasing advancement and malignancy of cancer cells. Obtained results encourage future clinical research and detailed chemical evaluation to specify the extract’s phytochemical composition. Full article

Campylobacter species are considered to be the leading bacterial cause of human gastroenteritis globally. Consumption of undercooked or contaminated food, such as chicken, is the main cause of human campylobacteriosis. Despite this significant zoonotic link, comparative data on virulence determinants in Campylobacter isolates across avian and human sources remain limited. This study aimed to characterize the prevalence and expression of virulence determinants in Campylobacter jejuni and Campylobacter coli isolates from chicken and human sources in Ismailia governorate, Egypt. A total of twenty C. jejuni and C. coli isolates (ten of each species) were screened for 14 virulence genes using PCR. All isolates harbored virB11, iam, racR, and tetO. Chicken isolates exhibited a significantly higher prevalence: C. jejuni (chicken): pldA, dnaJ, flaA (100%), cdtB (80%), ciaB (60%), and wlaN (0%); C. coli (chicken): pldA, dnaJ (100%), flaA (60%), cdtB (60%), ciaB (40%), and wlaN (20%). In contrast, human isolates showed a markedly lower prevalence: C. jejuni (human): dnaJ, flaA, and cdtB (20%); C. coli (human): dnaJ, flaA, and cdtB (40%). Crucially, pldA, ciaB, and wlaN were absent in all human isolates. plda and dnaJ genes showed statistically significant prevalence differences. qPCR revealed a significant upregulation (p < 0.05) of dnaJ, virB11, flaA, and iam in chicken isolates compared to human isolates, with log₂ fold changes of 3.52, 2.84, 2.43, and 1.90 for C. jejuni and 3.06, 2.38, 1.51, and 1.32 for C. coli. Differential expressions of racR, cdtB, and tetO were not significant, with log2 fold changes ranging from −0.51 to 0.14. Ganglioside mimicry genes (Cst11, wlaN, Waac, ggt, and cgtB) and the carbon storage regulator gene (csrA) were absent in all human isolates. These findings underscore the significant variability in virulence gene profiles in chicken and human C. jejuni and C. coli isolates and highlight the importance of molecular characterization in the risk assessment and epidemiological surveillance of Campylobacter infections. Full article

Background/Objectives: Osteoarthritis (OA) is a complex joint disease involving chronic inflammation, aging, and obesity, affecting nearly 6 million people worldwide. Senescent cells in OA are linked to increased inflammation, oxidative stress, and DNA damage, making them potential therapeutic targets. APPA, a combination of apocynin (AP) and paeonol (PA), has shown anti-inflammatory and antioxidant properties. This study evaluated the effects of APPA on cellular senescence in human articular chondrocytes. Methods: Using a chondrocyte cell line (T/C-28a2) and primary human chondrocytes, senescence was induced with etoposide and Oncostatin M (Eto + OSM), followed by treatment with APPA, AP, or PA. Senescence markers (SA-β-gal, P21_CDKN1A_), apoptosis, proliferation (Ki67), and rps6 protein levels were analyzed. Results: APPA significantly reduced SA-β-gal activity and p21 expression in cell model—effects not replicated by AP or PA alone. APPA increased early apoptosis and dual-labeled senescent-apoptotic cells, along with total cell numbers and rps6 levels. It also altered Ki67 expression in different cell subpopulations, suggesting effects on proliferation. Conclusions: This study suggests that APPA exerts senotherapeutic effects on human senescent chondrocytes. A reduction in SA-β-gal together with an increase in cell numbers and the proliferation marker Ki67 suggests possible senomorphic effects, whereas a reduction in SA-β-Gal accompanied by an increase in apoptosis indicates senolytic activity. These findings support recent evidence that the distinction between senolytic and senomorphic agents is ‘fuzzy’. Full article

Topoisomerase 1 (Top1) removes transcription-related helical torsions and thus plays an important role in preventing genome instability instigated by the formation of non-canonical DNA secondary structures. The genetically tractable Saccharomyces cerevisiae model proved effective in defining the critical function of Top1 to prevent recombination and chromosomal rearrangement at G4-forming genomic loci and studying the human cancer-associated Top1 mutants through the expression of analogous yeast mutants. We previously showed that cleavage-defective Top1 mutants strongly elevate the rate of recombination at G4 DNA, which involves binding to G4 DNA and interaction with the protein nucleolin (Nsr1 in yeast). Here, we further explored the mechanism of genome instability induced by the yeast Top1Y740* mutant, analogous to the human Top1W765Stop mutant conferring resistance to CPT. We show that yTop1Y740* elevates duplications as well as recombination specifically at G4-forming sequences. Interestingly, SUMOylation of yTop1Y740*, which does not affect the G4 DNA-binding or Nsr1-interaction by this mutant, is necessary for such elevated G4-specific genome instability. Many tumors with mutations at the C-terminal residues of Top1, particularly W765, have significantly high G4-associated mutations, underscoring the importance of further investigation into how SUMOylation affects the function of these Top1 mutants at G4 DNA. Full article

Skin cancer is the most common cancer worldwide. The incidence of skin cancer has been increasing worldwide. Nearly 75% of all skin cancers are basal cell carcinomas (BCC), cutaneous squamous cell carcinoma (cSCC) represents approximately 20%, and those remaining are melanomas (4%) or other rare tumors (1%). Given the high cure rates and the ability to histologically confirm tumor clearance, surgical therapy is the gold standard for the treatment of skin cancer. Conventional surgery is the most employed technique for the removal of non-melanoma skin cancer (NMSCs). Mohs Micrographic Surgery (MMS) is the most precise surgical method for the treatment of non-melanoma skin cancer, allowing for 100% margin evaluation, being the gold-standard method for surgical treatment of non-melanoma skin cancer. Whenever it is possible to obtain wide margins (4 to 6 mm), cure rates vary from 70% to 99%. Imiquimod, a synthetic imidazoquinolinone amine, is a topical immune response modifier approved by the U.S. Food and Drug Administration (FDA) for the treatment of external anogenital warts, actinic keratosis (AK), and superficial basal cell carcinoma (sBCC). The efficacy of imiquimod is primarily attributed to its ability to modulate both innate and adaptive immune responses, as well as its direct effects on cancer cells. Imiquimod exerts its immunomodulatory effects by activating Toll-like receptors 7 and 8 (TLR7/8) on various immune cells, including dendritic cells, macrophages, and natural killer (NK) cells. Upon binding to these receptors, imiquimod triggers the MyD88-dependent signaling pathway, leading to the activation of nuclear factor kappa B (NF-κB) and interferon regulatory factors (IRFs). This cascade leads to the production of pro-inflammatory cytokines, including interferon-alpha (IFN-α), tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-6 (IL-6). These cytokines enhance local inflammation, recruit additional immune cells to the tumor site, and stimulate antigen presentation, thereby promoting an anti-tumor immune response. Radiation therapy (RTh) may be employed as a primary treatment to BCC. It may also be employed as an adjuvant treatment to surgery for SCC and aggressive subtypes of BCC. RTh triggers both direct and indirect DNA damage on cancer cells and generates reactive oxygen species (ROS) within cells. ROS trigger oxidative damage to DNA, proteins, and lipids, exacerbating the cellular stress and contributing to tumor cell death. Recently, immunotherapy emerged as a revolutionary treatment for all stages of SCC. Cemiplimab is a human programmed cell death 1 (PD-1)-blocking antibody that triggers a response to over 50% of patients with locally advanced and metastatic SCC. A randomized clinical trial (RCT) published in 2022 revealed that cemiplimab was highly effective in the neoadjuvant treatment of large SCCs. The drug promoted a significant tumor size decrease, enabling organ-sparing operations and a much better cosmetic effect. A few months ago, a RCT of cemiplimab on adjuvant therapy for locally aggressive SCC was published. Interestingly, cemiplimab was administered to patients with local or regional cutaneous squamous cell carcinoma after surgical resection and postoperative radiotherapy, at high risk for recurrence owing to nodal features, revealed that cemiplimab led to much lower risks both of locoregional recurrence and distant recurrence. Full article

Core fucose is one of the most important glycans in HBV infection. In this study, we investigated whether Pholiota squarrosa lectin (PhoSL), a lectin that specifically binds to core fucose, exerts an inhibitory effect in an HBV infection model of normal human hepatocytes. Similarly to previous studies using hepatocellular carcinoma cells (HepG2-C4), the coexistence of PhoSL during HBV infection inhibited HBe antigen production and HBV cccDNA in normal human hepatocytes in a PhoSL concentration-dependent manner. Furthermore, this effect of PhoSL was found to be able to suppress HBe antigen production in a treatment period-dependent manner, even when PhoSL was administered after HBV infection. Our previous research has revealed that the mechanism by which PhoSL inhibits HBV infection is through physical inhibition by binding to the HBV receptor and inhibition of HBV entry into cells by inhibiting the phosphorylation of EGFR, a co-receptor for NTCP. Furthermore, this study suggested that PhoSL may also inhibit HBV proliferation in cells through other mechanisms that require further investigation. PhoSL is a lectin, derived from edible Pholiota squarrosa (shaggy scalycap) mushrooms, that is resistant to acid and heat. In addition, it has a low molecular weight and can be chemically synthesized, so it is expected to be used clinically as a new carbohydrate therapy for HBV in the future. Full article

Copaifera langsdorffii is a neotropical tree widely distributed in the Brazilian Atlantic Forest and Brazilian Savanna. Population genetic analyses can identify the scale at which tree species are impacted by human activities and provide useful demographic information for management and conservation. Using a Restriction site Associated DNA Sequencing approach, we assessed the genomic variability of six C. langsdorffii population relicts in a transition zone between the Seasonal Atlantic Forest and Savanna biomes in Southeastern Brazil. We identified 2797 high-confidence SNP markers from six remnant populations, with 10 to 29 individuals perpopulation, in a transition zone between the Seasonal Atlantic Forest and Savanna biomes in Southeastern Brazil. Observed heterozygosity values (0.197) were lower than expected heterozygosity (0.264) in all populations, indicating an excess of homozygotes. Differentiation among populations (F_ST) was low (0.023), but significant (0.007–0.044, c.i. 95%). A clear correlation was observed between geographic versus genetic distances, suggesting a pattern of isolation by distance. Bayesian inferences of population structure detected partial structuring due to the transition between the Atlantic Forest and the Brazilian Savanna, also suggested by spatial interpolation of ancestry coefficients. Through the analysis of F_ST outliers, 28 candidates for selection have been identified and may be associated with adaptation to these different phytophysiognomies. We conclude that the genetic variation found in these populations can be exploited in programs for the genetic conservation of the species. Full article