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ThPOK is a critical multifaceted regulator of myeloid lineagedevelopment.
Basu J. et al.
The transcription factor ThPOK (encoded by Zbtb7b) is well known for its role as a master regulator of CD4 lineage commitment in the thymus. Here, we report an unexpected and critical role of ThPOK as a multifaceted regulator of myeloid lineage commitment, differentiation and maturation. Using reporter and knockout ... |
Mediator 1 ablation induces enamel-to-hair lineage conversion in micethrough enhancer dynamics.
Thaler R. et al.
Postnatal cell fate is postulated to be primarily determined by the local tissue microenvironment. Here, we find that Mediator 1 (Med1) dependent epigenetic mechanisms dictate tissue-specific lineage commitment and progression of dental epithelia. Deletion of Med1, a key component of the Mediator complex linking enh... |
Supraphysiological Androgens Promote the Tumor Suppressive Activity of the Androgen Receptor Through cMYC Repression and Recruitment of the DREAM Complex
Nyquist M. et al.
The androgen receptor (AR) pathway regulates key cell survival programs in prostate epithelium. The AR represents a near-universal driver and therapeutic vulnerability in metastatic prostate cancer, and targeting AR has a remarkable therapeutic index. Though most approaches directed toward AR focus on inhibiting AR ... |
In skeletal muscle and neural crest cells, SMCHD1 regulates biologicalpathways relevant for Bosma syndrome and facioscapulohumeral dystrophyphenotype.
Laberthonnière C. et al.
Many genetic syndromes are linked to mutations in genes encoding factors that guide chromatin organization. Among them, several distinct rare genetic diseases are linked to mutations in SMCHD1 that encodes the structural maintenance of chromosomes flexible hinge domain containing 1 chromatin-associated factor. In hu... |
Vitamin D Receptor Cross-talk with p63 Signaling PromotesEpidermal Cell Fate.
Oda Y. et al.
The vitamin D receptor with its ligand 1,25 dihydroxy vitamin D (1,25D) regulates epidermal stem cell fate, such that VDR removal from Krt14 expressing keratinocytes delays re-epithelialization of epidermis after wound injury in mice. In this study we deleted Vdr from Lrig1 expressing stem cells in the isthmus of th... |
SOX expression in prostate cancer drives resistance to nuclear hormonereceptor signaling inhibition through the WEE1/CDK1 signaling axis.
Williams A. et al.
The development of androgen receptor signaling inhibitor (ARSI) drug resistance in prostate cancer (PC) remains therapeutically challenging. Our group has described the role of sex determining region Y-box 2 (SOX2) overexpression in ARSI-resistant PC. Continuing this work, we report that NR3C1, the gene encoding glu... |
Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsywith cataplexy.
Seifinejad A. et al.
Narcolepsy with cataplexy is a sleep disorder caused by deficiency in the hypothalamic neuropeptide hypocretin/orexin (HCRT), unanimously believed to result from autoimmune destruction of hypocretin-producing neurons. HCRT deficiency can also occur in secondary forms of narcolepsy and be only temporary, suggest... |
Activation of AKT induces EZH2-mediated β-catenin trimethylation incolorectal cancer.
Ghobashi A. H. et al.
Colorectal cancer (CRC) develops in part through the deregulation of different signaling pathways, including activation of the WNT/β-catenin and PI3K/AKT pathways. Enhancer of zeste homolog 2 (EZH2) is a lysine methyltransferase that is involved in regulating stem cell development and differentiation and is ove... |
Low affinity CTCF binding drives transcriptional regulation whereashigh affinity binding encompasses architectural functions
Marina-Zárate E. et al.
CTCF is a DNA-binding protein which plays critical roles in chromatin structure organization and transcriptional regulation; however, little is known about the functional determinants of different CTCF-binding sites (CBS). Using a conditional mouse model, we have identified one set of CBSs that are lost upon CTCF de... |
ZEB1 controls a lineage-specific transcriptional program essential formelanoma cell state transitions
Tang Y. et al.
Cell plasticity sustains intra-tumor heterogeneity and treatment resistance in melanoma. Deciphering the transcriptional mechanisms governing reversible phenotypic transitions between proliferative/differentiated and invasive/stem-like states is required in order to design novel therapeutic strategies. EMT-inducing ... |
A dataset of definitive endoderm and hepatocyte differentiations fromhuman induced pluripotent stem cells.
Tanaka Y. et al.
Hepatocytes are a major parenchymal cell type in the liver and play an essential role in liver function. Hepatocyte-like cells can be differentiated in vitro from induced pluripotent stem cells (iPSCs) via definitive endoderm (DE)-like cells and hepatoblast-like cells. Here, we explored the in vitro differentiation ... |
The mineralocorticoid receptor modulates timing and location of genomicbinding by glucocorticoid receptor in response to synthetic glucocorticoidsin keratinocytes.
Carceller-Zazo E. et al.
Glucocorticoids (GCs) exert potent antiproliferative and anti-inflammatory properties, explaining their therapeutic efficacy for skin diseases. GCs act by binding to the GC receptor (GR) and the mineralocorticoid receptor (MR), co-expressed in classical and non-classical targets including keratinocytes. Using knocko... |
In vitro production of cat-restricted Toxoplasma pre-sexual stages byepigenetic reprogramming
Antunes A. V.et al.
Sexual reproduction of , which is restricted to the small intestine of felids, is sparsely documented, due to ethical concerns surrounding the use of cats as model organisms. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cis... |
A Systemic and Integrated Analysis of p63-Driven RegulatoryNetworks in Mouse Oral Squamous Cell Carcinoma.
Glathar A. R. et al.
Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and is linked to tobacco exposure, alcohol consumption, and human papillomavirus infection. Despite therapeutic advances, a lack of molecular understanding of disease etiology, and delayed diagnoses continue to negatively affect sur... |
The aryl hydrocarbon receptor cell intrinsically promotes resident memoryCD8 T cell differentiation and function.
Dean J. W. et al.
The Aryl hydrocarbon receptor (Ahr) regulates the differentiation and function of CD4 T cells; however, its cell-intrinsic role in CD8 T cells remains elusive. Herein we show that Ahr acts as a promoter of resident memory CD8 T cell (T) differentiation and function. Genetic ablation of Ahr in mouse CD... |
Impact of Fetal Exposure to Endocrine Disrupting ChemicalMixtures on FOXA3 Gene and Protein Expression in Adult RatTestes.
Walker C. et al.
Perinatal exposure to endocrine disrupting chemicals (EDCs) has been shown to affect male reproductive functions. However, the effects on male reproduction of exposure to EDC mixtures at doses relevant to humans have not been fully characterized. In previous studies, we found that in utero exposure to mixtures of th... |
Expression of RNA polymerase I catalytic core is influenced byRPA12.
Ford B. L. et al.
RNA Polymerase I (Pol I) has recently been recognized as a cancer therapeutic target. The activity of this enzyme is essential for ribosome biogenesis and is universally activated in cancers. The enzymatic activity of this multi-subunit complex resides in its catalytic core composed of RPA194, RPA135, and RPA12, a s... |
Identification of an E3 ligase that targets the catalytic subunit ofRNA polymerase I upon transcription stress.
Pitts Stephanie et al.
RNA polymerase I (Pol I) synthesizes ribosomal RNA (rRNA), which is the first and rate-limiting step in ribosome biogenesis. Factors governing the stability of the polymerase complex are not known. Previous studies characterizing the Pol I inhibitor BMH-21 revealed a transcriptional stress-dependent pathway for degr... |
Histone Deacetylases 1 and 2 target gene regulatory networks of nephronprogenitors to control nephrogenesis.
Liu Hongbing et al.
Our studies demonstrated the critical role of Histone deacetylases (HDACs) in the regulation of nephrogenesis. To better understand the key pathways regulated by HDAC1/2 in early nephrogenesis, we performed chromatin immunoprecipitation sequencing (ChIP-Seq) of Hdac1/2 on isolated nephron progenitor cells (NPCs) fro... |
Identification of genomic binding sites and direct target genes for thetranscription factor DDIT3/CHOP.
Osman A. et al.
DDIT3 is a tightly regulated basic leucine zipper (bZIP) transcription factor and key regulator in cellular stress responses. It is involved in a variety of pathological conditions and may cause cell cycle block and apoptosis. It is also implicated in differentiation of some specialized cell types and as an oncogene... |
Androgen-Induced MIG6 Regulates Phosphorylation ofRetinoblastoma Protein and AKT to Counteract Non-Genomic ARSignaling in Prostate Cancer Cells.
Schomann T. et al.
The bipolar androgen therapy (BAT) includes the treatment of prostate cancer (PCa) patients with supraphysiological androgen level (SAL). Interestingly, SAL induces cell senescence in PCa cell lines as well as ex vivo in tumor samples of patients. The SAL-mediated cell senescence was shown to be androgen receptor (A... |
Co-inhibition of ATM and ROCK synergistically improves cellproliferation in replicative senescence by activating FOXM1 and E2F1.
Yang Eun Jae et al.
The multifaceted nature of senescent cell cycle arrest necessitates the targeting of multiple factors arresting or promoting the cell cycle. We report that co-inhibition of ATM and ROCK by KU-60019 and Y-27632, respectively, synergistically increases the proliferation of human diploid fibroblasts undergoing replicat... |
Derailed peripheral circadian genes in polycystic ovary syndrome patientsalters peripheral conversion of androgens synthesis.
Johnson B.S. et al.
STUDY QUESTION: Do circadian genes exhibit an altered profile in peripheral blood mononuclear cells (PBMCs) of polycystic ovary syndrome (PCOS) patients and do they have a potential role in androgen excess? SUMMARY ANSWER: Our findings revealed that an impaired circadian clock could hamper the regulation of peripher... |
GATA6 is predicted to regulate DNA methylation in an in vitro model ofhuman hepatocyte differentiation.
Suzuki T. et al.
Hepatocytes are the dominant cell type in the human liver, with functions in metabolism, detoxification, and producing secreted proteins. Although gene regulation and master transcription factors involved in the hepatocyte differentiation have been extensively investigated, little is known about how the epigenome is... |
A systematic comparison of FOSL1, FOSL2 and BATF-mediatedtranscriptional regulation during early human Th17 differentiation.
Shetty A. et al.
Th17 cells are essential for protection against extracellular pathogens, but their aberrant activity can cause autoimmunity. Molecular mechanisms that dictate Th17 cell-differentiation have been extensively studied using mouse models. However, species-specific differences underscore the need to validate these findin... |
An obesogenic feedforward loop involving PPARγ, acyl-CoA bindingprotein and GABA receptor.
Anagnostopoulos Gerasimos et al.
Acyl-coenzyme-A-binding protein (ACBP), also known as a diazepam-binding inhibitor (DBI), is a potent stimulator of appetite and lipogenesis. Bioinformatic analyses combined with systematic screens revealed that peroxisome proliferator-activated receptor gamma (PPARγ) is the transcription factor that best expl... |
Transient regulation of focal adhesion via Tensin3 is required fornascent oligodendrocyte differentiation
Merour E. et al.
The differentiation of oligodendroglia from oligodendrocyte precursor cells (OPCs) to complex and extensive myelinating oligodendrocytes (OLs) is a multistep process that involves largescale morphological changes with significant strain on the cytoskeleton. While key chromatin and transcriptional regulators of diffe... |
Characteristics of Immediate-Early 2 (IE2) and UL84 Proteins in UL84-Independent Strains of Human Cytomegalovirus (HCMV)
Salome Manska and Cyprian C Rossetto
Human cytomegalovirus (HCMV) immediate-early 2 (IE2) protein is the major transactivator for viral gene expression and is required for lytic replication. In addition to transcriptional activation, IE2 is known to mediate transcriptional repression of promoters, including the major immediate-early (MIE) promoter and ... |
Essential role of a ThPOK autoregulatory loop in the maintenance ofmature CD4 T cell identity and function.
Basu Jayati et al.
The transcription factor ThPOK (encoded by the Zbtb7b gene) controls homeostasis and differentiation of mature helper T cells, while opposing their differentiation to CD4 intraepithelial lymphocytes (IELs) in the intestinal mucosa. Thus CD4 IEL differentiation requires ThPOK transcriptional repression via reactivati... |
Environmental enrichment preserves a young DNA methylation landscape inthe aged mouse hippocampus
Zocher S. et al.
The decline of brain function during aging is associated with epigenetic changes, including DNA methylation. Lifestyle interventions can improve brain function during aging, but their influence on age-related epigenetic changes is unknown. Using genome-wide DNA methylation sequencing, we here show that experiencing ... |
Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment.
Pettinato, Anthony M. et al.
Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization by unclear mechanisms. To study this process, we engineer a human cardiomyocyte model to track replication and polyploidization using fluorescently tagged cyclin B1 and cardiac troponin T. Using time-lapse i... |
VPRBP functions downstream of the androgen receptor and OGT to restrict p53 activation in prostate cancer
Poulose N. et al.
Androgen receptor (AR) is a major driver of prostate cancer (PCa) initiation and progression. O-GlcNAc transferase (OGT), the enzyme that catalyses the covalent addition of UDP-N-acetylglucosamine (UDP-GlcNAc) to serine and threonine residues of proteins, is often up-regulated in PCa with its expression correlated w... |
BAF complexes drive proliferation and block myogenic differentiation in fusion-positive rhabdomyosarcoma
Laubscher et. al.
Rhabdomyosarcoma (RMS) is a pediatric malignancy of skeletal muscle lineage. The aggressive alveolar subtype is characterized by t(2;13) or t(1;13) translocations encoding for PAX3- or PAX7-FOXO1 chimeric transcription factors, respectively, and are referred to as fusion positive RMS (FP-RMS). The fusion gene alters... |
The epigenetic regulator RINF (CXXC5) maintains SMAD7 expression in human immature erythroid cells and sustains red blood cellsexpansion.
Astori A. et al.
The gene CXXC5, encoding a Retinoid-Inducible Nuclear Factor (RINF), is located within a region at 5q31.2 commonly deleted in myelodysplastic syndrome (MDS) and adult acute myeloid leukemia (AML). RINF may act as an epigenetic regulator and has been proposed as a tumor suppressor in hematopoietic malignancies. Howev... |
ΔNp63 is a pioneer factor that binds inaccessible chromatin and elicitchromatin remodeling
Yu X. et al.
Background: ΔNp63 is a master transcriptional regulator playing critical roles in epidermal development and other cellular processes. Recent studies suggest that ΔNp63 functions as a pioneer factor that can target its binding sites within inaccessible chromatin and induce chromatin remodeling. Methods: I... |
Battle of the sex chromosomes: competition between X- and Y-chromosomeencoded proteins for partner interaction and chromatin occupancy drivesmulti-copy gene expression and evolution in muroid rodents.
Moretti, C and Blanco, M and Ialy-Radio, C and Serrentino, ME and Gobé,C and Friedman, R and Battail, C and Leduc, M and Ward, MA and Vaiman, Dand Tores, F and Cocquet, J
Transmission distorters (TDs) are genetic elements that favor their own transmission to the detriments of others. Slx/Slxl1 (Sycp3-like-X-linked and Slx-like1) and Sly (Sycp3-like-Y-linked) are TDs which have been co-amplified on the X and Y chromosomes of Mus species. They are involved in an intragenomic conflict i... |
Dysregulation of BRD4 Function Underlies the Functional Abnormalities of MeCP2 Mutant Neurons.
Xiang Y, Tanaka Y, Patterson B, Hwang SM, Hysolli E, Cakir B, Kim KY, Wang W, Kang YJ, Clement EM, Zhong M, Lee SH, Cho YS, Patra P, Sullivan GJ, Weissman SM, Park IH
Rett syndrome (RTT), mainly caused by mutations in methyl-CpG binding protein 2 (MeCP2), is one of the most prevalent intellectual disorders without effective therapies. Here, we used 2D and 3D human brain cultures to investigate MeCP2 function. We found that MeCP2 mutations cause severe abnormalities in human inter... |
MYC transcription activation mediated by OCT4 as a mechanism of resistance to 13-cisRA-mediated differentiation in neuroblastoma.
Wei SJ, Nguyen TH, Yang IH, Mook DG, Makena MR, Verlekar D, Hindle A, Martinez GM, Yang S, Shimada H, Reynolds CP, Kang MH
Despite the improvement in clinical outcome with 13-cis-retinoic acid (13-cisRA) + anti-GD2 antibody + cytokine immunotherapy given in first response ~40% of high-risk neuroblastoma patients die of recurrent disease. MYCN genomic amplification is a biomarker of aggressive tumors in the childhood cancer neuroblastoma... |
CRISPR off-target detection with DISCOVER-seq.
Wienert B, Wyman SK, Yeh CD, Conklin BR, Corn JE
DISCOVER-seq (discovery of in situ Cas off-targets and verification by sequencing) is a broadly applicable approach for unbiased CRISPR-Cas off-target identification in cells and tissues. It leverages the recruitment of DNA repair factors to double-strand breaks (DSBs) after genome editing with CRISPR nucleases. Her... |
LncRNA np_5318 promotes renal ischemia‑reperfusion injury through the TGF‑β/Smad signaling pathway
Lu Jing , Miao Jiangang , Sun Jianhua
Long noncoding (Lnc)RNA np_5318 has been proved to be involved in renal injury, while its functionality in renal ischemia‑reperfusion (I/R) injury is unknown. Therefore, the present study aimed to investigate the role of lncRNA np_5318 in the development of renal I/R injury. Renal I/R injury model and I/R cell model... |
Pro-death signaling of cytoprotective heat shock factor 1: upregulation of NOXA leading to apoptosis in heat-sensitive cells.
Janus P, Toma-Jonik A, Vydra N, Mrowiec K, Korfanty J, Chadalski M, Widłak P, Dudek K, Paszek A, Rusin M, Polańska J, Widłak W
Heat shock can induce either cytoprotective mechanisms or cell death. We found that in certain human and mouse cells, including spermatocytes, activated heat shock factor 1 (HSF1) binds to sequences located in the intron(s) of the PMAIP1 (NOXA) gene and upregulates its expression which induces apoptosis. Such a mode... |
17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells.
Vydra N, Janus P, Toma-Jonik A, Stokowy T, Mrowiec K, Korfanty J, Długajczyk A, Wojtaś B, Gielniewski B, Widłak W
Heat Shock Factor 1 (HSF1) is a key regulator of gene expression during acute environmental stress that enables the cell survival, which is also involved in different cancer-related processes. A high level of HSF1 in estrogen receptor (ER)-positive breast cancer patients correlated with a worse prognosis. Here we de... |
Cooperation of cancer drivers with regulatory germline variants shapes clinical outcomes.
Musa J, Cidre-Aranaz F, Aynaud MM, Orth MF, Knott MML, Mirabeau O, Mazor G, Varon M, Hölting TLB, Grossetête S, Gartlgruber M, Surdez D, Gerke JS, Ohmura S, Marchetto A, Dallmayer M, Baldauf MC, Stein S, Sannino G, Li J, Romero-Pérez L, Westermann F, Hart
Pediatric malignancies including Ewing sarcoma (EwS) feature a paucity of somatic alterations except for pathognomonic driver-mutations that cannot explain overt variations in clinical outcome. Here, we demonstrate in EwS how cooperation of dominant oncogenes and regulatory germline variants determine tumor growth, ... |
The Toxoplasma effector TEEGR promotes parasite persistence by modulating NF-κB signalling via EZH2.
Braun L, Brenier-Pinchart MP, Hammoudi PM, Cannella D, Kieffer-Jaquinod S, Vollaire J, Josserand V, Touquet B, Couté Y, Tardieux I, Bougdour A, Hakimi MA
The protozoan parasite Toxoplasma gondii has co-evolved with its homeothermic hosts (humans included) strategies that drive its quasi-asymptomatic persistence in hosts, hence optimizing the chance of transmission to new hosts. Persistence, which starts with a small subset of parasites that escape host immune killing... |
Preformed chromatin topology assists transcriptional robustness of during limb development.
Paliou C, Guckelberger P, Schöpflin R, Heinrich V, Esposito A, Chiariello AM, Bianco S, Annunziatella C, Helmuth J, Haas S, Jerković I, Brieske N, Wittler L, Timmermann B, Nicodemi M, Vingron M, Mundlos S, Andrey G
Long-range gene regulation involves physical proximity between enhancers and promoters to generate precise patterns of gene expression in space and time. However, in some cases, proximity coincides with gene activation, whereas, in others, preformed topologies already exist before activation. In this study, we inves... |
NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma.
Hegde GV, de la Cruz C, Giltnane JM, Crocker L, Venkatanarayan A, Schaefer G, Dunlap D, Hoeck JD, Piskol R, Gnad F, Modrusan Z, de Sauvage FJ, Siebel CW, Jackson EL
Squamous cell carcinomas (SCCs) account for the majority of cancer mortalities. Although TP63 is an established lineage-survival oncogene in SCCs, therapeutic strategies have not been developed to target TP63 or it's downstream effectors. In this study we demonstrate that TP63 directly regulates NRG1 expression in h... |
Guidelines for optimized gene knockout using CRISPR/Cas9
Campenhout CV et al.
CRISPR/Cas9 technology has evolved as the most powerful approach to generate genetic models both for fundamental and preclinical research. Despite its apparent simplicity, the outcome of a genome-editing experiment can be substantially impacted by technical parameters and biological considerations. Here, we present ... |
Maintenance of MYC expression promotes de novo resistance to BET bromodomain inhibition in castration-resistant prostate cancer.
Coleman DJ, Gao L, Schwartzman J, Korkola JE, Sampson D, Derrick DS, Urrutia J, Balter A, Burchard J, King CJ, Chiotti KE, Heiser LM, Alumkal JJ
The BET bromodomain protein BRD4 is a chromatin reader that regulates transcription, including in cancer. In prostate cancer, specifically, the anti-tumor activity of BET bromodomain inhibition has been principally linked to suppression of androgen receptor (AR) function. MYC is a well-described BRD4 target gene in ... |
Crosstalk Between Glucocorticoid Receptor and Early-growth Response Protein 1 Accounts for Repression of Brain-derived Neurotrophic Factor Transcript 4 Expression.
Chen H, Amazit L, Lombès M, Le Menuet D
The brain-derived neurotrophic factor (BDNF) is a key player in brain functions such as synaptic plasticity, stress, and behavior. Its gene structure in rodents contains 8 untranslated exons (I to VIII) whose expression is finely regulated and which spliced onto a common and unique translated exon IX. Altered Bdnf e... |
Glucocorticoids stimulate hypothalamic dynorphin expression accounting for stress-induced impairment of GnRH secretion during preovulatory period.
Ayrout M, Le Billan F, Grange-Messent V, Mhaouty-Kodja S, Lombès M, Chauvin S
Stress-induced reproductive dysfunction is frequently associated with increased glucocorticoid (GC) levels responsible for suppressed GnRH/LH secretion and impaired ovulation. Besides the major role of the hypothalamic kisspeptin system, other key regulators may be involved in such regulatory mechanisms. Herein, we ... |
Epigenetic Co-Deregulation of EZH2/TET1 is a Senescence-Countering, Actionable Vulnerability in Triple-Negative Breast Cancer.
Yu Y, Qi J, Xiong J, Jiang L, Cui D, He J, Chen P, Li L, Wu C, Ma T, Shao S, Wang J, Yu D, Zhou B, Huang D, Schmitt CA, Tao R
Triple-negative breast cancer (TNBC) cells lack the expression of ER, PR and HER2. Thus, TNBC patients cannot benefit from hormone receptor-targeted therapy as non-TNBC patients, but can only receive chemotherapy as the systemic treatment and have a worse overall outcome. More effective therapeutic targets and combi... |
The long noncoding RNA and nuclear paraspeckles are up-regulated by the transcription factor HSF1 in the heat shock response.
Lellahi SM, Rosenlund IA, Hedberg A, Kiær LT, Mikkola I, Knutsen E, Perander M
The long noncoding RNA (lncRNA) (nuclear enriched abundant transcript 1) is the architectural component of nuclear paraspeckles, and it has recently gained considerable attention as it is abnormally expressed in pathological conditions such as cancer and neurodegenerative diseases. and paraspeckle formation are incr... |
Aryl Hydrocarbon Receptor Signaling Cell Intrinsically Inhibits Intestinal Group 2 Innate Lymphoid Cell Function.
Li S, Bostick JW, Ye J, Qiu J, Zhang B, Urban JF, Avram D, Zhou L
Innate lymphoid cells (ILCs) are important for mucosal immunity. The intestine harbors all ILC subsets, but how these cells are balanced to achieve immune homeostasis and mount appropriate responses during infection remains elusive. Here, we show that aryl hydrocarbon receptor (Ahr) expression in the gut regulates I... |
RRAD, IL4I1, CDKN1A, and SERPINE1 genes are potentially co-regulated by NF-κB and p53 transcription factors in cells exposed to high doses of ionizing radiation.
Szołtysek K, Janus P, Zając G, Stokowy T, Walaszczyk A, Widłak W, Wojtaś B, Gielniewski B, Cockell S, Perkins ND, Kimmel M, Widlak P
BACKGROUND: The cellular response to ionizing radiation involves activation of p53-dependent pathways and activation of the atypical NF-κB pathway. The crosstalk between these two transcriptional networks include (co)regulation of common gene targets. Here we looked for novel genes potentially (co)regulated by... |
H3K4me2 and WDR5 enriched chromatin interacting long non-coding RNAs maintain transcriptionally competent chromatin at divergent transcriptional units.
Subhash S, Mishra K, Akhade VS, Kanduri M, Mondal T, Kanduri C
Recently lncRNAs have been implicated in the sub-compartmentalization of eukaryotic genome via genomic targeting of chromatin remodelers. To explore the function of lncRNAs in the maintenance of active chromatin, we characterized lncRNAs from the chromatin enriched with H3K4me2 and WDR5 using chromatin RNA immunopre... |
The long non-coding RNA NEAT1 and nuclear paraspeckles are upregulated by the transcription factor HSF1 in the heat shock response.
Lellahi SM, Rosenlund IA, Hedberg A, Kiær LT, Mikkola I, Knutsen E, Perander M
The long non-coding RNA (lncRNA) NEAT1 is the architectural component of nuclear paraspeckles, and has recently gained considerable attention as it is abnormally expressed in pathological conditions such as cancer and neurodegenerative diseases. NEAT1 and paraspeckle formation are increased in cells upon expos... |
ΔNp63-driven recruitment of myeloid-derived suppressor cells promotes metastasis in triple-negative breast cancer.
Kumar S, Wilkes DW, Samuel N, Blanco MA, Nayak A, Alicea-Torres K, Gluck C, Sinha S, Gabrilovich D, Chakrabarti R
Triple-negative breast cancer (TNBC) is particularly aggressive, with enhanced incidence of tumor relapse, resistance to chemotherapy, and metastases. As the mechanistic basis for this aggressive phenotype is unclear, treatment options are limited. Here, we showed an increased population of myeloid-derived immunosup... |
FACT Sets a Barrier for Cell Fate Reprogramming in Caenorhabditis elegans and Human Cells.
Kolundzic E, Ofenbauer A, Bulut SI, Uyar B, Baytek G, Sommermeier A, Seelk S, He M, Hirsekorn A, Vucicevic D, Akalin A, Diecke S, Lacadie SA, Tursun B
The chromatin regulator FACT (facilitates chromatin transcription) is essential for ensuring stable gene expression by promoting transcription. In a genetic screen using Caenorhabditis elegans, we identified that FACT maintains cell identities and acts as a barrier for transcription factor-mediated cell fate reprogr... |
The Alzheimer's disease-associated TREM2 gene is regulated by p53 tumor suppressor protein.
Zajkowicz A, Gdowicz-Kłosok A, Krześniak M, Janus P, Łasut B, Rusin M
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