Putative looping factor ZNF143/ZFP143 is an essential transcriptional regulator with no looping function.

Narducci, Domenic N, and Anders S Hansen. 2025. “Putative Looping Factor ZNF143/ZFP143 Is an Essential Transcriptional Regulator With No Looping Function.”. Molecular Cell 85 (1): 9-23.e9.

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Abstract

Interactions between distal loci, including those involving enhancers and promoters, are a central mechanism of gene regulation in mammals, yet the protein regulators of these interactions remain largely undetermined. The zinc-finger transcription factor (TF) ZNF143/ZFP143 has been strongly implicated as a regulator of chromatin interactions, functioning either with or without CTCF. However, how ZNF143/ZFP143 functions as a looping factor is not well understood. Here, we tagged both CTCF and ZNF143/ZFP143 with dual-purpose degron/imaging tags to combinatorially assess their looping function and effect on each other. We find that ZNF143/ZFP143, contrary to prior reports, possesses no general looping function in mouse and human cells and that it largely functions independently of CTCF. Instead, ZNF143/ZFP143 is an essential and highly conserved transcription factor that largely binds promoters proximally, exhibits an extremely stable chromatin dwell time (>20 min), and regulates an important subset of mitochondrial and ribosomal genes.

Last updated on 08/28/2025
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Yeum, Dabin, Timothy J Renier, Travis D Masterson, Delaina D Carlson, Grace A Ballarino, Reina K Lansigan, Ruth J F Loos, Jennifer A Emond, and Diane Gilbert-Diamond. (2025) 2025. “Genetic Associations With Consumption of Palatable Foods in the Absence of Hunger in Response to Food Cues in Children.”. Pediatric Obesity 20 (4): e13168. https://doi.org/10.1111/ijpo.13168.

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OBJECTIVE: The objective of this study is to evaluate obesity-related genetic factors in relation to excess consumption and assess if food cues modify associations.
METHODS: Children (9-12 years) completed a randomized crossover experiment. During two visits, children ate a preload and then snacks ad libitum while watching television, embedded with food or non-food advertisements to assess eating in the absence of hunger (EAH). Primary exposures were obesity-associated genotypes, FTO rs9939609 and MC4R rs571312, and a paediatric-specific polygenic risk score (PRS). Outcomes included consumption of all snacks (total EAH) and gummy candy only (gummy candy EAH). Linear mixed-effects models tested whether genetic exposures related to EAH outcomes. We tested for effect modification by food cues using multiplicative interaction terms.
RESULTS: Among 177 children, each FTO risk allele was associated with a 30% increase in gummy candy EAH (p = 0.025) in adjusted models. Food cue exposure exacerbated associations between the FTO variant with gummy candy EAH (p = 0.046). No statistically significant associations were found between MC4R and EAH.
CONCLUSION: The results suggest children with the FTO rs9939609 risk allele may be predisposed to excess consumption of candy and that this association may be exacerbated by food cues.
Dall, Morten, Katharina Herzog, Antonia Hufnagel, Daniel B Ibsen, Benjamin Lebiecka-Johansen, Philip M M Ruppert, Jessica M Preston, Pearlyn J Y Toh, and Christina Yfanti. (2025) 2025. “Our Future, We Decide: Five Ways to Reform the Scientific Publication Process.”. Nature Reviews. Endocrinology 21 (1): 5-6. https://doi.org/10.1038/s41574-024-01056-x.

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Höring, Marcus, Sarah Brunner, Josef Scheiber, Julius Honecker, Gerhard Liebisch, Claudine Seeliger, Laura Schinhammer, et al. (2025) 2025. “Sex-Specific Response of the Human Plasma Lipidome to Short-Term Cold Exposure.”. Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids 1870 (1): 159567. https://doi.org/10.1016/j.bbalip.2024.159567.

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Cold-induced lipolysis is widely studied as a potential therapeutic strategy to combat metabolic disease, but its effect on lipid homeostasis in humans remains largely unclear. Blood plasma comprises an enormous repertoire in lipids allowing insights into whole body lipid homeostasis. So far, reported results originate from studies carried out with small numbers of male participants. Here, the blood plasma's lipidome of 78 male and 93 female volunteers, who were exposed to cold below the shivering threshold for 2 h, was quantified by comprehensive lipidomics using high-resolution mass spectrometry. Short-term cold exposure increased the concentrations in 147 of 177 quantified circulating lipids and the response of the plasma's lipidome was sex-specific. In particular, the amounts of generated glycerophospholipid and sphingolipid species differed between the sexes. In women, the BMI could be related with the lipidome's response. A logistic regression model predicted with high sensitivity and specificity whether plasma samples were from male or female subjects based on the cold-induced response of phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and sphingomyelin (SM) species. In summary, cold exposure promotes lipid synthesis by supplying fatty acids generated after lipolysis for all lipid classes. The plasma lipidome, i.e. PC, LPC and SM, shows a sex-specific response, indicating a different regulation of its metabolism in men and women. This supports the need for sex-specific research and avoidance of sex bias in clinical trials.
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The complete blood count (CBC) is an important screening tool for healthy adults and a common test at periodic exams. However, results are usually interpreted relative to one-size-fits-all reference intervals1,2, undermining the precision medicine goal to tailor care for patients on the basis of their unique characteristics3,4. Here we study thousands of diverse patients at an academic medical centre and show that routine CBC indices fluctuate around stable values or setpoints5, and setpoints are patient-specific, with the typical healthy adult's nine CBC setpoints distinguishable as a group from those of 98% of other healthy adults, and setpoint differences persist for at least 20 years. Haematological setpoints reflect a deep physiologic phenotype enabling investigation of acquired and genetic determinants of haematological regulation and its variation among healthy adults. Setpoints in apparently healthy adults were associated with significant variation in clinical risk: absolute risk of some common diseases and morbidities varied by more than 2% (heart attack and stroke, diabetes, kidney disease, osteoporosis), and absolute risk of all-cause 10 year mortality varied by more than 5%. Setpoints also define patient-specific reference intervals and personalize the interpretation of subsequent test results. In retrospective analysis, setpoints improved sensitivity and specificity for evaluation of some common conditions including diabetes, kidney disease, thyroid dysfunction, iron deficiency and myeloproliferative neoplasms. This study shows CBC setpoints are sufficiently stable and patient-specific to help realize the promise of precision medicine for healthy adults.
Yeum, Dabin, Timothy J Renier, Travis D Masterson, Delaina D Carlson, Grace A Ballarino, Reina K Lansigan, Ruth J F Loos, Jennifer A Emond, and Diane Gilbert-Diamond. (2025) 2025. “Genetic Associations With Consumption of Palatable Foods in the Absence of Hunger in Response to Food Cues in Children.”. Pediatric Obesity 20 (4): e13168. https://doi.org/10.1111/ijpo.13168.

Publisher's Version

OBJECTIVE: The objective of this study is to evaluate obesity-related genetic factors in relation to excess consumption and assess if food cues modify associations.
METHODS: Children (9-12 years) completed a randomized crossover experiment. During two visits, children ate a preload and then snacks ad libitum while watching television, embedded with food or non-food advertisements to assess eating in the absence of hunger (EAH). Primary exposures were obesity-associated genotypes, FTO rs9939609 and MC4R rs571312, and a paediatric-specific polygenic risk score (PRS). Outcomes included consumption of all snacks (total EAH) and gummy candy only (gummy candy EAH). Linear mixed-effects models tested whether genetic exposures related to EAH outcomes. We tested for effect modification by food cues using multiplicative interaction terms.
RESULTS: Among 177 children, each FTO risk allele was associated with a 30% increase in gummy candy EAH (p = 0.025) in adjusted models. Food cue exposure exacerbated associations between the FTO variant with gummy candy EAH (p = 0.046). No statistically significant associations were found between MC4R and EAH.
CONCLUSION: The results suggest children with the FTO rs9939609 risk allele may be predisposed to excess consumption of candy and that this association may be exacerbated by food cues.
Dall, Morten, Katharina Herzog, Antonia Hufnagel, Daniel B Ibsen, Benjamin Lebiecka-Johansen, Philip M M Ruppert, Jessica M Preston, Pearlyn J Y Toh, and Christina Yfanti. (2025) 2025. “Our Future, We Decide: Five Ways to Reform the Scientific Publication Process.”. Nature Reviews. Endocrinology 21 (1): 5-6. https://doi.org/10.1038/s41574-024-01056-x.

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Osteoid osteoma (OO) is a common, benign bone tumor. However, there are no case reports of OO associated with osteogenesis imperfecta (OI), or pathological fractures in OO. A 3-year-old girl with OI sustained a complete right tibial diaphyseal fracture. Bony fusion was completed after 4 months of conservative therapy; nevertheless, 18 months later spontaneous pain appeared at the fracture site, without any cause. Plain radiographs showed a newly apparent, rounded area of translucency 1 cm in diameter, just overlapping the previous fracture. Images obtained using three-dimensional time-resolved contrast-enhanced magnetic resonance angiography showed strong central enhancement in the early phase, with an apparent nidus, suggesting the diagnosis of OO. Nineteen months after the first fracture, while skipping, the patient refractured her tibial diaphysis at the site of the previous fracture. This is a very rare case of OO, apparently co-existing with OI and leading to a bony fracture. In our case, the combination of bone fragility in OI and a recent fracture at the site of the OO may have caused the re-fracture.
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This work combines functional studies in model systems and examination of human tumor specimens to define a central oncogenic pathway driven by DNAJB1-PRKACA fusions in FLC. DNAJB1-PRKACA-mediated inactivation of the SIK stimulates CRTC2-p300-mediated transcription to drive tumor growth. The findings illuminate pathogenic mechanisms and inform therapeutic development.
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Eating disorders (EDs) commonly co-occur with other psychiatric and neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD); however, the pattern of family history and genetic overlap among them requires clarification. This study investigated the diagnostic, familial, and genetic associations of EDs with ADHD and ASD. The nationwide population-based cohort study included all individuals born in Denmark, 1981-2008, linked to their siblings and cousins. Cox regression was used to estimate associations between EDs and ADHD or ASD, and mediation analysis was used to assess the effects of intermediate mood or anxiety disorders. Polygenic scores (PGSs) were used to investigate the genetic association between anorexia nervosa (AN) and ADHD or ASD. Significantly increased risk for any ED was observed following an ADHD or ASD diagnosis. Mediation analysis suggested that intermediate mood or anxiety disorders could account for 44%-100% of the association between ADHD or ASD and ED. Individuals with a full sibling or maternal half sibling with ASD had increased risk of AN compared to those with siblings without ASD. A positive association was found between ASD-PGS and AN risk whereas a negative association was found between AN-PGS and ADHD. In this study, positive phenotypic associations between EDs and ADHD or ASD, mediation by mood or anxiety disorder, and genetic associations between ASD-PGS and AN and between AN-PGS and ADHD were observed. These findings could guide future research in the development of new treatments that can mitigate the development of EDs among individuals with ADHD or ASD.