Digital Commons Network^™

Identification Of Lysosomal Lipolysis As An Essential Noncanonical Mediator Of Adipocyte Fasting And Cold-Induced Lipolysis, Yu-Sheng Yeh, Trent D. Evans, Mari Iwase, Se-Jin Jeong, Arick Park, Ali Ghasemian, Borna Dianati, Ali Javaheri, Et Al.

2020-Current year OA Pubs

Adipose tissue lipolysis is the process by which triglycerides in lipid stores are hydrolyzed into free fatty acids (FFAs), serving as fuel during fasting or cold-induced thermogenesis. Although cytosolic lipases are considered the predominant mechanism of liberating FFAs, lipolysis also occurs in lysosomes via lysosomal acid lipase (LIPA), albeit with unclear roles in lipid storage and whole-body metabolism. We found that adipocyte LIPA expression increased in adipose tissue of mice when lipolysis was stimulated during fasting, cold exposure, or β-adrenergic agonism. This was functionally important, as inhibition of LIPA genetically or pharmacologically resulted in lower plasma FFAs under lipolytic conditions. …

High-Throughput Repurposing Screen Reveals Compounds With Activity Against Toxoplasma Gondii Bradyzoites, Taher Uddin, Jing Xia, Yong Fu, Case W Mcnamara, Arnab K Chatterjee, L David Sibley

2020-Current year OA Pubs

No abstract provided.

Proteome-Wide Analysis Of Autoantibodies In Open-Angle Glaucoma In Japanese Population: A Pilot Study, Naoko Takada, Yukitoshi Izumi, Charles F Zorumski, Et Al.

2020-Current year OA Pubs

No abstract provided.

C10-Benzoate Esters Of Anhydrotetracycline Inhibit Tetracycline Destructases And Recover Tetracycline Antibacterial Activity, Emily E Williford, Yao-Peng Xue, Wai Kwan Tang, Ruihao Li, Katherine V Jones, Kevin S Blake, Helen C Blaine, Xiang Lian, Christina L Stallings, Niraj H Tolia, Gautam Dantas, Timothy A Wencewicz

2020-Current year OA Pubs

Tetracyclines (TCs) are an important class of antibiotics threatened by enzymatic inactivation. These tetracycline-inactivating enzymes, also known as tetracycline destructases (TDases), are a subfamily of class A flavin monooxygenases (FMOs) that catalyze hydroxyl group transfer and oxygen insertion (Baeyer-Villiger type) reactions on TC substrate scaffolds. Semisynthetic modification of TCs (e.g., tigecycline, omadacycline, eravacycline, and sarecycline) has proven effective in evading certain resistance mechanisms, such as ribosomal protection and efflux, but does not protect against TDase-mediated resistance. Here, we report the design, synthesis, and evaluation of a new series of 22 semisynthetic TDase inhibitors that explore D-ring substitution of anhydrotetracycline (aTC) …

Expression Of A Single Inhibitory Member Of The Ly49 Receptor Family Is Sufficient To License Nk Cells For Effector Functions, Sytse J Piersma, Shasha Li, Pamela Wong, Michael D Bern, Jennifer Poursine-Laurent, Li-Ping Yang, Diana L Beckman, Bijal A Parikh, Wayne M Yokoyama

2020-Current year OA Pubs

Natural killer (NK) cells recognize target cells through germline-encoded activation and inhibitory receptors enabling effective immunity against viruses and cancer. The Ly49 receptor family in the mouse and killer immunoglobin-like receptor family in humans play a central role in NK cell immunity through recognition of major histocompatibility complex class I (MHC-I) and related molecules. Functionally, these receptor families are involved in the licensing and rejection of MHC-I-deficient cells through missing-self. The Ly49 family is highly polymorphic, making it challenging to detail the contributions of individual Ly49 receptors to NK cell function. Herein, we showed mice lacking expression of all Ly49s …

Altered Joint Forces Found In Symptomatic Dysplastic Hips In Women During Sport-Specific Activities, Molly C Shepherd, Rannon Huo, John C Clohisy, Jeffrey J Nepple, Michael Harris

2020-Current year OA Pubs

BACKGROUND: Many patients with developmental dysplasia of the hip (DDH) are young and highly active but often become limited by activity-induced pain. Characterizing how the abnormal bony geometry of DDH affects hip joint loading and multiplanar kinematics during sport-specific motions relevant to active patients may provide insight into injury mechanisms and inform optimal treatment options.

PURPOSE/HYPOTHESIS: The purpose of this study was to determine how hip joint loading and kinematics are altered in DDH during 2 common sport activities: running and multidirectional hop-cutting. It was hypothesized that superior and medial joint-reaction forces (JRFs) would be elevated during running and that …

Differences In Plasma Metabolome Between Non-Hispanic White And Non-Hispanic Black Women, Ghazaleh Pourali, Liang Li, Myung Sik Jeon, Jingqin Luo, Chongliang Luo, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: To understand potential racial differences in disease susceptibility and develop targeted prevention strategies, it is essential to establish biological differences between racial groups in healthy individuals. However, knowledge about how race impacts metabolites is limited. We therefore performed a cross-sectional study using comprehensive metabolomics analysis to investigate racial differences in metabolites among 506 non-Hispanic White (NHW) women and 163 non-Hispanic Black (NHB) women.

METHODS: We performed untargeted plasma metabolomic profiling using Metabolon's platform (Durham, NC®) and identified 1074 metabolites in 9 super-pathways. We used multivariable linear regression models, adjusted for confounders, to identify associations between race and metabolites. We …

Structural Basis For Dimerization And Activation Of Uvrd-Family Helicases, Ankita Chadda, Binh Nguyen, Timothy M Lohman, Eric A Galburt

2020-Current year OA Pubs

UvrD-family helicases are superfamily 1A motor proteins that function during DNA replication, recombination, repair, and transcription. UvrD family monomers translocate along single-stranded (ss) DNA but need to be activated by dimerization to unwind DNA in the absence of force or accessory factors. However, prior structural studies have only revealed monomeric complexes. Here, we report the first structures of a dimeric UvrD-family helicase,

Transcriptome Complexity Disentangled: A Regulatory Molecules Approach, Amir Asiaee, Zachary B Abrams, Heather H Pua, Kevin R Coombes

2020-Current year OA Pubs

Transcription factors (TFs) and microRNAs (miRNAs) are fundamental regulators of gene expression, cell state, and biological processes. This study investigated whether a small subset of TFs and miRNAs could accurately predict genome-wide gene expression. We analyzed 8895 samples across 31 cancer types from The Cancer Genome Atlas and identified 28 miRNA and 28 TF clusters using unsupervised learning. Medoids of these clusters could differentiate tissues of origin with 92.8% accuracy, demonstrating their biological relevance. We developed Tissue-Agnostic and Tissue-Aware models to predict 20,000 gene expressions using the 56 selected medoid miRNAs and TFs. The Tissue-Aware model attained an R2 of …

Nad+ Prevents Chronic Kidney Disease By Activating Renal Tubular Metabolism, Bryce A. Jones, Sanjay Jain, Et Al.

2020-Current year OA Pubs

Chronic kidney disease (CKD) is associated with renal metabolic disturbances, including impaired fatty acid oxidation (FAO). Nicotinamide adenine dinucleotide (NAD+) is a small molecule that participates in hundreds of metabolism-related reactions. NAD+ levels are decreased in CKD, and NAD+ supplementation is protective. However, both the mechanism of how NAD+ supplementation protects from CKD, as well as the cell types involved, are poorly understood. Using a mouse model of Alport syndrome, we show that nicotinamide riboside (NR), an NAD+ precursor, stimulated renal PPARα signaling and restored FAO in the proximal tubules, thereby protecting from CKD in both sexes. Bulk RNA-sequencing showed …

Apobec3a Drives Ovarian Cancer Metastasis By Altering Epithelial-Mesenchymal Transition, Jessica M. Devenport, Thi Tran, Brooke R. Harris, Dylan Fingerman, Rachel A. Deweerd, Lojain H. Elkhidir, Danielle Lavigne, Katherine Fuh, Lulu Sun, Jeffrey J. Bednarski, Ronny Drapkin, Mary M. Mullen, Abby M. Green

2020-Current year OA Pubs

High-grade serous ovarian cancer (HGSOC) is the most prevalent and aggressive histological subtype of ovarian cancer and often presents with metastatic disease. The drivers of metastasis in HGSOC remain enigmatic. APOBEC3A (A3A), an enzyme that generates mutations across various cancers, has been proposed as a mediator of tumor heterogeneity and disease progression. However, the role of A3A in HGSOC has not been explored. We observed an association between high levels of APOBEC3-mediated mutagenesis and poor overall survival in primary HGSOC. We experimentally addressed this correlation by modeling A3A expression in HGSOC, and this resulted in increased metastatic behavior of HGSOC …

Augmented Expression Of Superoxide Dismutase 2 Mitigates Progression And Rupture Of Experimental Abdominal Aortic Aneurysm, Huimin Yan, Ying Hu, Yang Lyu, Antonina Akk, Angela C Hirbe, Samuel A Wickline, Hua Pan, Elisha D O Roberson, Christine T N Pham

2020-Current year OA Pubs

No abstract provided.

Investigating The Impact Of Electroconvulsive Therapy On Brain Networks And Sleep: An Observational Study Protocol, Mohammadmehdi Kafashan, Lucas Lebovitz, Robby Greenspan, Sijia Zhao, Tae Kim, Masud Husain, Tamara Hershey, Pilar Cristancho, R Edward Hogan, Ben Julian Agustin Palanca, Nuri B Farber, Dns-Ect Study Team

2020-Current year OA Pubs

INTRODUCTION: Electroconvulsive therapy (ECT) is a highly effective treatment for refractory depression, but it may also cause cognitive side effects. Despite decades of use, the mechanisms by which ECT exerts both its antidepressant and cognitive effects are still poorly understood, with the latter substantially limiting referral and adherence to therapy. ECT induces changes in correlated neural activity-functional connectivity-across various brain networks, which may underlie both its clinical efficacy and associated cognitive side effects. Electroencephalography (EEG) could address these knowledge gaps by identifying biomarkers that predict therapeutic outcomes or cognitive side effects. Such developments could ultimately improve patient selection and adherence. …

Kir7.1 Is The Physiological Target For Hormones And Steroids That Regulate Uteroplacental Function, Monika Haoui, Citlalli Vergara, Lina Kenzler, Jerome Schröer, Geraldine Zimmer-Bensch, David Fleck, Christopher Wiesbrock, Marc Spehr, Polina V Lishko

2020-Current year OA Pubs

Preterm birth is detrimental to the well-being of both the mother and the newborn. During normal gestation, the myometrium is maintained in a quiescent state by progesterone. As a steroid hormone, progesterone is thought to modify uterine and placental morphology by altering gene expression, but another direct mode of action has long been suspected. Here, we reveal the nongenomic molecular mechanism of progesterone as the activation of human and murine inwardly rectifying potassium channel Kir7.1, which is expressed in myometrium and placental pericytes during late gestation. Kir7.1 is also activated by selective steroids, including those used to prevent premature labor, …

Non-Invasive Assessment Of Vascular Damage Through Pulse Wave Velocity And Superb Microvascular Imaging In Pre-Dialysis Patients, Julia Martín-Vírgala, Beatriz Martín-Carro, Sara Fernández-Villabrille, Belinda Fernández-Mariño, Elena Astudillo-Cortés, Minerva Rodríguez-García, Carmen Díaz-Corte, José Luis Fernández-Martín, Carlos Gómez-Alonso, Adriana S Dusso, Cristina Alonso-Montes, Manuel Naves-Díaz, Sara Panizo, Natalia Carrillo-López

2020-Current year OA Pubs

No abstract provided.

Sex Differences In Apolipoprotein E And Alzheimer Disease Pathology Across Ancestries, Xiaoyi Xu, Jiseon Kwon, Ruiqi Yan, Catherine Apio, Soomin Song, Gyujin Heo, Qijun Yang, Jigyasha Timsina, Menghan Liu, John Budde, John C Morris, Carlos Cruchaga, Yun Ju Sung, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Age, sex, and apolipoprotein E (APOE) are the strongest risk factors for late-onset Alzheimer disease (AD). The role of APOE in AD varies with sex and ancestry. While the association of APOE with AD biomarkers also varies across sex and ancestry, no study has systematically investigated both sex-specific and ancestry differences of APOE on cerebrospinal fluid (CSF) biomarkers together, resulting in limited insights and generalizability.

OBJECTIVE: To systematically investigate the association of sex and APOE-ε4 with 3 core CSF biomarkers across ancestries.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined 3 CSF biomarkers (amyloid β1-42 [Aβ42], phosphorylated tau 181 …

Racial Equity In Urine Drug Screening Policies In Labor And Delivery, Vahid Azimi, Cassandra Trammel, Lauren Nacke, Alexandra Rubin, Lori Stevenson, Brittaney Vaughn, Stephen M Roper, Mark A Zaydman, Ronald Jackups, Noor Riaz, Kim P Schamel, Jeannie C Kelly

2020-Current year OA Pubs

IMPORTANCE: Black pregnant patients are significantly more likely than their White counterparts to undergo peripartum urine drug screening (UDS) and subsequent reporting to child protective services (CPS).

OBJECTIVE: To evaluate the association of removing isolated cannabis use and limited prenatal care as order indications, combined with clinician-facing clinical decision support, with racial parity in peripartum UDS and CPS reporting.

DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study assessed 9396 pregnant patients at a single tertiary care center in a Midwestern US urban metropolitan region who delivered before (June 1, 2021, to September 31, 2022) and after (October 1, 2022, to …

Environmental Hygiene Strategies To Combat Antimicrobial Resistance In Healthcare Settings, Mary Morgan Lee, Caroline A O'Neil, Lucy Vogt, Jennie H Kwon

2020-Current year OA Pubs

In this manuscript, we highlight current literature on environmental hygiene techniques to combat reservoirs of antibiotic resistant organisms in the healthcare environment. We discuss several topics for each strategy, including mechanism of action, assessment of effectiveness based on studies, cost, and real-world translatability. The techniques and topics summarized here are not inclusive of all available environmental hygiene techniques but highlight some of the more popular and investigated strategies. We focus on the following: Ultraviolet radiation, hydrogen peroxide vapor, copper-coated surfaces, phages, interventions involving sinks, and educational initiatives.

Endothelial Cell Piezo1 Promotes Vascular Smooth Muscle Cell Differentiation On Large Arteries, Javier Abello, Ying Yin, Yonghui Zhao, Josh Maurer, Jihui Lee, Cherokee Bodell, Jahmiera Richee, Zarek Burton, Megan E Goeckel, Michelle Lin, Carmen M Halabi, Rajan Sah, Amber N Stratman, Et Al.

2020-Current year OA Pubs

Vascular stabilization is a mechanosensitive process, in part driven by blood flow. Here, we demonstrate the involvement of the mechanosensitive ion channel, Piezo1, in promoting arterial accumulation of vascular smooth muscle cells (vSMCs) during zebrafish development. Using a series of small molecule antagonists or agonists to temporally regulate Piezo1 activity, we identified a role for the Piezo1 channel in regulating klf2a, a blood flow responsive transcription factor, expression levels and altered targeting of vSMCs between arteries and veins. Increasing Piezo1 activity suppressed klf2a and increased vSMC association with the cardinal vein, while inhibition of Piezo1 activity increased klf2a levels and …

Reward Neurocircuitry Predicts Longitudinal Changes In Alcohol Use Following Trauma Exposure, Cecilia A Hinojosa, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: Trauma is a risk factor for developing maladaptive alcohol use. Preclinical research has shown that stress alters the processing of midbrain and striatal reward and incentive signals. However, little research has been conducted on alterations in reward-related neurocircuitry posttrauma in humans. Neuroimaging markers may be particularly useful because they can provide insight into the mechanisms that may make an individual vulnerable to developing trauma-related psychopathologies. In this study, we aimed to identify reward-related neural correlates associated with changes in alcohol use after trauma exposure.

METHODS: Participants were recruited from U.S. emergency departments for the AURORA study (n = 286; …

The Single-Cell Immune Profile Throughout Gestation And Its Potential Value For Identifying Women At Risk For Spontaneous Preterm Birth, Dorien Feyaerts, Maïgane Diop, Jose Galaz, Jakob F Einhaus, Petra C Arck, Anke Diemert, Virginia D Winn, Mana Parast, Cynthia Gyamfi-Bannerman, Jelmer R Prins, Nardhy Gomez-Lopez, Ina A Stelzer

2020-Current year OA Pubs

Precisely timed immune adaptations, observed in the maternal circulation, underpin the notion of an immune clock of human pregnancy that supports its successful progression and completion at delivery. This immune clock is divided into three immunological phases, with the first phase starting at the time of conception and implantation, shifting into the second phase that supports homeostasis and tolerance throughout pregnancy, and culminating in the last phase of labor and parturition. Disruptions of this immune clock are reported in pregnancy complications such as spontaneous preterm birth. However, our understanding of the immune clock preceding spontaneous preterm birth remains scattered. In …

Genomics Of Pediatric Cardiomyopathy, Teresa M Lee, Stephanie M Ware, Alicia M Kamsheh, Surbhi Bhatnagar, Mohammed Absi, Elyse Miller, Enkhsaikhan Purevjav, Kaitlin A Ryan, Jeffrey A Towbin, Steven E Lipshultz

2020-Current year OA Pubs

Cardiomyopathy in children is a leading cause of heart failure and cardiac transplantation. Disease-associated genetic variants play a significant role in the development of the different subtypes of disease. Genetic testing is increasingly being recognized as the standard of care for diagnosing this heterogeneous group of disorders, guiding management, providing prognostic information, and facilitating family-based risk stratification. The increase in clinical and research genetic testing within the field has led to new insights into this group of disorders. Mutations in genes encoding sarcomere, cytoskeletal, Z-disk, and sarcolemma proteins appear to play a major role in causing the overlapping clinical phenotypes …

Loncastuximab In High-Risk And Heavily Pretreated Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Real-World Analysis From 21 Us Centers, Viktoriya Zelikson, Behzad Amoozgar, Brad Kahl, Et Al.

2020-Current year OA Pubs

Outcomes in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) are poor. Loncastuximab- teserine (Lonca) is an antibody-drug conjugate which was approved by the Food and Drug Administration for the treatment of patients with R/R DLBCL who have received at least two prior lines of therapy, based on the results of the LOTIS-2 trial. However, there are limited data regarding its efficacy in the real-world setting. This retrospective study included 21 US centers and evaluated outcomes of patients with R/R DLBCL treated with Lonca. Our analysis comprises 187 patients with notably higher-risk baseline features compared to those of the …

Parameterizing Toxic Stress In Early Childhood: Maternal Depression, Maltreatment, And Hpa-Axis Variation In A Pilot Intervention Study, Rachael E Wagner, Melissa Jonson-Reid, Brett Drake, Patricia L Kohl, Laura Pons, Yi Zhang, Robert T Fitzgerald, Mark L Laudenslager, John N Constantino

2020-Current year OA Pubs

Adverse experiences superseding a child's capacity to sustain regulation of emotion and adaptive function are theorized to constitute "toxic stressors" when they induce a deleterious biological response within an individual. We ascertained presumptive parameters of toxic stress among 164 low-income infants and toddlers (ages 4-48 months) from 132 families enrolled in Early Head Start (EHS). We randomized a subset of these families into a pilot intervention arm of parenting education (the Incredible Years, TIY), which supplemented the EHS curriculum. Official report child abuse and neglect (CAN) and child behavior were serially ascertained over the course of the study. We observed …

Genetically Engineered Brain Organoids Recapitulate Spatial And Developmental States Of Glioblastoma Progression, Matthew Ishahak, Rowland H Han, Devi Annamalai, Timothy Woodiwiss, Colin Mccornack, Ryan T Cleary, Patrick A Desouza, Xuan Qu, Sonika Dahiya, Albert H Kim, Jeffrey R Millman

2020-Current year OA Pubs

Glioblastoma (GBM) is an aggressive form of brain cancer that is highly resistant to therapy due to significant intra-tumoral heterogeneity. The lack of robust in vitro models to study early tumor progression has hindered the development of effective therapies. Here, this study develops engineered GBM organoids (eGBOs) harboring GBM subtype-specific oncogenic mutations to investigate the underlying transcriptional regulation of tumor progression. Single-cell and spatial transcriptomic analyses revealed that these mutations disrupt normal neurodevelopment gene regulatory networks resulting in changes in cellular composition and spatial organization. Upon xenotransplantation into immunodeficient mice, eGBOs form tumors that recapitulate the transcriptional and spatial landscape …

Relationships Between Brain Glucose Metabolism Patterns And Impaired Glycemic Status: A Systematic Review Of Fdg-Pet Studies With A Focus On Alzheimer's Disease, Setareh Soltani, Mahsa Dolatshahi, Sara Soltani, Kian Khazaei, Maryam Rahmani, Cyrus A Raji

2020-Current year OA Pubs

It is well-established that individuals with type 2 diabetes have an increased risk of developing cognitive impairment and Alzheimer's disease (AD). However, it is not fully determined how insulin resistance and type 2 diabetes are related to AD-related brain glucose metabolism abnormalities. For this aim, we performed a systematic review of the studies investigating the association between cerebral glucose metabolism and glycemic status, including diabetes, insulin resistance, or hyperglycemia. Medline, Embase, and Cochrane databases were searched (till February 2, 2025). All English full-text papers studying 18F-FDG-PET that investigated the association between cerebral FDG uptake or cerebral metabolism rate and glycemic …

Spatial Histomorphometry Reveals That Local Peripheral Nerves Modulate But Are Not Required For Skeletal Adaptation To Applied Load In Mice, Alec T Beeve, Mohamed G Hassan, Anna Li, Nicole Migotsky, Matthew J Silva, Erica L Scheller

2020-Current year OA Pubs

Mechanical loading is required for bone health and results in skeletal adaptation to optimize strength. Local nerve axons, particularly within the periosteum, may respond to load-induced biomechanical and biochemical cues. However, their role in the bone anabolic response remains controversial. We hypothesized that spatial alignment of periosteal nerves with sites of load-induced bone formation would clarify this relationship. To achieve this, we developed RadialQuant, a custom tool for spatial histomorphometry. Tibiae of control and neurectomized (sciatic/femoral nerve cut) pan-neuronal Baf53b-tdTomato reporter mice were loaded for 5 days. Bone formation and periosteal nerve axon density were then quantified simultaneously in non-decalcified …

Prognostic, Biological, And Structural Implications Of Flt3-Jmd Point Mutations In Acute Myeloid Leukemia: An Analysis Of Alliance Studies, Nadeen Anabtawi, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

The FLT3 gene frequently undergoes mutations in acute myeloid leukemia (AML), with internal tandem duplications (ITD) and tyrosine kinase domain (TKD) point mutations (PMs) being most common. Recently, PMs and deletions in the FLT3 juxtamembrane domain (JMD) have been identified, but their biological and clinical significance remains poorly understood. We analyzed 1660 patients with de novo AML and found FLT3-JMD mutations, mostly PMs, in 2% of the patients. Patients with FLT3-JMD mutations had a higher relapse rate and shorter disease-free survival than those with FLT3-TKD, whereas their relapse rate, disease-free and overall survival were not significantly different from those of …

Acute Hyperglycemia Induces Podocyte Apoptosis By Monocyte Tnf-Α Release, A Process Attenuated By Vitamin D And Glp-1 Receptor Agonists, Rong M Zhang, Jisu Oh, Burton M Wice, Adriana Dusso, Carlos Bernal-Mizrachi

2020-Current year OA Pubs

Targeting optimal glycemic control based on hemoglobin A1c (A1c) values reduces but does not abolish the onset of diabetic kidney disease and its progression to chronic kidney disease (CKD). This suggests that factors other than the average glucose contribute to the residual risk. Vitamin D deficiency and frequent episodes of acute hyperglycemia (AH) are associated with the onset of albuminuria and CKD progression in diabetes. This study aimed to determine if moderate levels of AH harm podocytes directly or promote a pro-inflammatory monocyte/macrophage phenotype that leads to podocyte apoptosis, and whether vitamin D deficiency accelerates these processes. We found that …

Integrative Analysis Of The 3d Genome And Epigenome In Mouse Embryonic Tissues, Miao Yu, Yang E Li, Et Al.

2020-Current year OA Pubs

While a rich set of putative cis-regulatory sequences involved in mouse fetal development have been annotated recently on the basis of chromatin accessibility and histone modification patterns, delineating their role in developmentally regulated gene expression continues to be challenging. To fill this gap, here we mapped chromatin contacts between gene promoters and distal sequences across the genome in seven mouse fetal tissues and across six developmental stages of the forebrain. We identified 248,620 long-range chromatin interactions centered at 14,138 protein-coding genes and characterized their tissue-to-tissue variations and developmental dynamics. Integrative analysis of the interactome with previous epigenome and transcriptome datasets …