abstract：:The physiological functions of many vital tissues and organs continue to mature after birth, but the genetic mechanisms governing this postnatal maturation remain an unsolved mystery. Human pancreatic β cells produce and secrete insulin in response to physiological cues like glucose, and these hallmark functions impro...

journal_title：Genes & development

authors： Bevacqua RJ,Lam JY,Peiris H,Whitener RL,Kim S,Gu X,Friedlander MSH,Kim SK

更新日期：2021-01-14 00:00:00

abstract：:Transcriptionally silent genes must be activated throughout development. This requires nucleosomes be removed from promoters and enhancers to allow transcription factor (TF) binding and recruitment of coactivators and RNA polymerase II (Pol II). Specialized pioneer TFs bind nucleosome-wrapped DNA to perform this chrom...

journal_title：Genes & development

authors： Judd J,Duarte FM,Lis JT

更新日期：2021-01-01 00:00:00

abstract：:Gene duplication and divergence is a major driver in the emergence of evolutionary novelties. How variations in amino acid sequences lead to loss of ancestral activity and functional diversification of proteins is poorly understood. We used cross-species functional analysis of Drosophila Labial and its mouse HOX1 orth...

journal_title：Genes & development

authors： Singh NP,De Kumar B,Paulson A,Parrish ME,Zhang Y,Florens L,Conaway JW,Si K,Krumlauf R

更新日期：2020-12-01 00:00:00

abstract：:Atypical teratoid rhabdoid tumors (ATRTs) are challenging pediatric brain cancers that are predominantly associated with inactivation of the gene SMARCB1, a conserved subunit of the chromatin remodeling BAF complex, which has known contributions to developmental processes. To identify potential interactions between SM...

journal_title：Genes & development

authors： Parisian AD,Koga T,Miki S,Johann PD,Kool M,Crawford JR,Furnari FB

更新日期：2020-10-01 00:00:00

abstract：:Identifying modifiers of dosage-sensitive genes involved in neurodegenerative disorders is imperative to discover novel genetic risk factors and potential therapeutic entry points. In this study, we focus on Ataxin-1 (ATXN1), a dosage-sensitive gene involved in the neurodegenerative disease spinocerebellar ataxia type...

journal_title：Genes & development

authors： Nitschke L,Tewari A,Coffin SL,Xhako E,Pang K,Gennarino VA,Johnson JL,Blanco FA,Liu Z,Zoghbi HY

更新日期：2020-09-01 00:00:00

abstract：:Small cell lung cancer (SCLC) is an aggressive neuroendocrine cancer characterized by initial chemosensitivity followed by emergence of chemoresistant disease. To study roles for MYCN amplification in SCLC progression and chemoresistance, we developed a genetically engineered mouse model of MYCN-overexpressing SCLC. I...

journal_title：Genes & development

authors： Grunblatt E,Wu N,Zhang H,Liu X,Norton JP,Ohol Y,Leger P,Hiatt JB,Eastwood EC,Thomas R,Ibrahim AH,Jia D,Basom R,Eaton KD,Martins R,Houghton AM,MacPherson D

更新日期：2020-09-01 00:00:00

abstract：:Nonsense-mediated decay (NMD) is a translation-dependent RNA quality control mechanism that occurs in the cytoplasm. However, it is unknown how NMD regulates the stability of RNAs translated at the endoplasmic reticulum (ER). Here, we identify a localized NMD pathway dedicated to ER-translated mRNAs. We previously ide...

journal_title：Genes & development

authors： Longman D,Jackson-Jones KA,Maslon MM,Murphy LC,Young RS,Stoddart JJ,Hug N,Taylor MS,Papadopoulos DK,Cáceres JF

更新日期：2020-08-01 00:00:00

abstract：:Transcription by RNA polymerase II (RNAPII) is a dynamic process with frequent variations in the elongation rate. However, the physiological relevance of variations in RNAPII elongation kinetics has remained unclear. Here we show in yeast that a RNAPII mutant that reduces the transcription elongation rate causes wides...

journal_title：Genes & development

authors： Yague-Sanz C,Vanrobaeys Y,Fernandez R,Duval M,Larochelle M,Beaudoin J,Berro J,Labbé S,Jacques PÉ,Bachand F

更新日期：2020-07-01 00:00:00

abstract：:RNA polymerase II (Pol II) transcribes all protein-coding genes and many noncoding RNAs in eukaryotic genomes. Although Pol II is a complex, 12-subunit enzyme, it lacks the ability to initiate transcription and cannot consistently transcribe through long DNA sequences. To execute these essential functions, an array of...

journal_title：Genes & development

authors： Schier AC,Taatjes DJ

更新日期：2020-04-01 00:00:00

abstract：:Cellular senescence is a potent tumor suppressor mechanism but also contributes to aging and aging-related diseases. Senescence is characterized by a stable cell cycle arrest and a complex proinflammatory secretome, termed the senescence-associated secretory phenotype (SASP). We recently discovered that cytoplasmic ch...

journal_title：Genes & development

authors： Vizioli MG,Liu T,Miller KN,Robertson NA,Gilroy K,Lagnado AB,Perez-Garcia A,Kiourtis C,Dasgupta N,Lei X,Kruger PJ,Nixon C,Clark W,Jurk D,Bird TG,Passos JF,Berger SL,Dou Z,Adams PD

更新日期：2020-03-01 00:00:00

abstract：:Centromeres are maintained epigenetically by the presence of CENP-A, an evolutionarily conserved histone H3 variant, which directs kinetochore assembly and hence centromere function. To identify factors that promote assembly of CENP-A chromatin, we affinity-selected solubilized fission yeast CENP-ACnp1 chromatin. All ...

journal_title：Genes & development

authors： Singh PP,Shukla M,White SA,Lafos M,Tong P,Auchynnikava T,Spanos C,Rappsilber J,Pidoux AL,Allshire RC

更新日期：2020-02-01 00:00:00

abstract：:Genomic imprinting is an epigenetic phenomenon leading to parentally biased gene expression. Throughout the years, extensive efforts have been made to characterize the epigenetic marks underlying imprinting in animals and plants. As a result, DNA methylation asymmetries between parental genomes emerged as the primary ...

journal_title：Genes & development

authors： Batista RA,Köhler C

更新日期：2020-01-01 00:00:00

abstract：:The allosteric and torpedo models have been used for 30 yr to explain how transcription terminates on protein-coding genes. The former invokes termination via conformational changes in the transcription complex and the latter proposes that degradation of the downstream product of poly(A) signal (PAS) processing is imp...

journal_title：Genes & development

authors： Eaton JD,Francis L,Davidson L,West S

更新日期：2020-01-01 00:00:00

abstract：:TGF-β receptors phosphorylate SMAD2 and SMAD3 transcription factors, which then form heterotrimeric complexes with SMAD4 and cooperate with context-specific transcription factors to activate target genes. Here we provide biochemical and structural evidence showing that binding of SMAD2 to DNA depends on the conformati...

journal_title：Genes & development

authors： Aragón E,Wang Q,Zou Y,Morgani SM,Ruiz L,Kaczmarska Z,Su J,Torner C,Tian L,Hu J,Shu W,Agrawal S,Gomes T,Márquez JA,Hadjantonakis AK,Macias MJ,Massagué J

更新日期：2019-11-01 00:00:00

abstract：:The ubiquitin-specific protease (USP) family is the largest group of cysteine proteases. Cancer genomic analysis identified frequent amplification of USP21 (22%) in human pancreatic ductal adenocarcinoma (PDAC). USP21 overexpression correlates with human PDAC progression, and enforced expression of USP21 accelerates m...

journal_title：Genes & development

authors： Hou P,Ma X,Zhang Q,Wu CJ,Liao W,Li J,Wang H,Zhao J,Zhou X,Guan C,Ackroyd J,Jiang S,Zhang J,Spring DJ,Wang YA,DePinho RA

更新日期：2019-10-01 00:00:00

abstract：:Although MAX is regarded as an obligate dimerization partner for MYC, its function in normal development and neoplasia is poorly defined. We show that B-cell-specific deletion of Max has a modest effect on B-cell development but completely abrogates Eµ-Myc-driven lymphomagenesis. While Max loss affects only a few hund...

journal_title：Genes & development

authors： Mathsyaraja H,Freie B,Cheng PF,Babaeva E,Catchpole JT,Janssens D,Henikoff S,Eisenman RN

更新日期：2019-09-01 00:00:00

abstract：:All transcription factors are equal, but some are more equal than others. In the 25 yr since the gene encoding the microphthalmia-associated transcription factor (MITF) was first isolated, MITF has emerged as a key coordinator of many aspects of melanocyte and melanoma biology. Like all transcription factors, MITF bin...

journal_title：Genes & development

authors： Goding CR,Arnheiter H

更新日期：2019-08-01 00:00:00

abstract：:Gene dosage alterations caused by aneuploidy are a common feature of most cancers yet pose severe proteotoxic challenges. Therefore, cells have evolved various dosage compensation mechanisms to limit the damage caused by the ensuing protein level imbalances. For instance, for heteromeric protein complexes, excess nons...

journal_title：Genes & development

authors： Samant RS,Masto VB,Frydman J

更新日期：2019-08-01 00:00:00

abstract：:Mammalian development requires effective mechanisms to repress genes whose expression would generate inappropriately specified cells. The Polycomb-repressive complex 1 (PRC1) family complexes are central to maintaining this repression. These include a set of canonical PRC1 complexes, each of which contains four core p...

journal_title：Genes & development

authors： Plys AJ,Davis CP,Kim J,Rizki G,Keenen MM,Marr SK,Kingston RE

更新日期：2019-07-01 00:00:00

abstract：:The balance between proliferation and differentiation of muscle stem cells is tightly controlled, ensuring the maintenance of a cellular pool needed for muscle growth and repair. We demonstrate here that the transcriptional regulator Hes1 controls the balance between proliferation and differentiation of activated musc...

journal_title：Genes & development

authors： Lahmann I,Bröhl D,Zyrianova T,Isomura A,Czajkowski MT,Kapoor V,Griger J,Ruffault PL,Mademtzoglou D,Zammit PS,Wunderlich T,Spuler S,Kühn R,Preibisch S,Wolf J,Kageyama R,Birchmeier C

更新日期：2019-05-01 00:00:00

abstract：:The RNA polymerase II (RNAPII) C-terminal domain kinase, CDK12, regulates genome stability, expression of DNA repair genes, and cancer cell resistance to chemotherapy and immunotherapy. In addition to its role in mRNA biosynthesis of DNA repair genes, we show here that CDK12 phosphorylates the mRNA 5' cap-binding repr...

journal_title：Genes & development

authors： Choi SH,Martinez TF,Kim S,Donaldson C,Shokhirev MN,Saghatelian A,Jones KA

更新日期：2019-04-01 00:00:00

abstract：:Genomic imprinting is an epigenetic mechanism by which genes are expressed in a parental origin-dependent manner. We recently discovered that, like DNA methylation, oocyte-inherited H3K27me3 can also serve as an imprinting mark in mouse preimplantation embryos. In this study, we found H3K27me3 is strongly biased towar...

journal_title：Genes & development

authors： Zhang W,Chen Z,Yin Q,Zhang D,Racowsky C,Zhang Y

更新日期：2019-04-01 00:00:00

abstract：:Genomic imprinting is an epigenetic process regulated by germline-derived DNA methylation, causing parental origin-specific monoallelic gene expression. Zinc finger protein 57 (ZFP57) is critical for maintenance of this epigenetic memory during post-fertilization reprogramming, yet incomplete penetrance of ZFP57 mutat...

journal_title：Genes & development

authors： Takahashi N,Coluccio A,Thorball CW,Planet E,Shi H,Offner S,Turelli P,Imbeault M,Ferguson-Smith AC,Trono D

更新日期：2019-01-01 00:00:00

abstract：:Genomic imprinting is essential for mammalian development. Recent studies have revealed that maternal histone H3 Lys27 trimethylation (H3K27me3) can mediate DNA methylation-independent genomic imprinting. However, the regulatory mechanisms and functions of this new imprinting mechanism are largely unknown. Here we dem...

journal_title：Genes & development

authors： Inoue A,Chen Z,Yin Q,Zhang Y

更新日期：2018-12-01 00:00:00

abstract：:Estrogen receptor α (ER) is the major driver of ∼75% of breast cancers, and multiple ER targeting drugs are routinely used clinically to treat patients with ER+ breast cancer. However, many patients relapse on these targeted therapies and ultimately develop metastatic and incurable disease, and understanding the mecha...

journal_title：Genes & development

authors： Siersbæk R,Kumar S,Carroll JS

更新日期：2018-09-01 00:00:00

abstract：:The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is known to regulate lipid metabolism in many tissues, including macrophages. Here we report that peritoneal macrophage respiration is enhanced by rosiglitazone, an activating PPARγ ligand, in a PPARγ-dependent manner. Moreover, PPARγ is require...

journal_title：Genes & development

authors： Nelson VL,Nguyen HCB,Garcìa-Cañaveras JC,Briggs ER,Ho WY,DiSpirito JR,Marinis JM,Hill DA,Lazar MA

更新日期：2018-08-01 00:00:00

abstract：:The senescence-associated secretory phenotype (SASP) is a major trait of senescent cells, but the molecular regulators of SASP factor secretion are poorly understood. Mass spectrometry analysis revealed that secretory carrier membrane protein 4 (SCAMP4) levels were strikingly elevated on the surface of senescent cells...

journal_title：Genes & development

authors： Kim KM,Noh JH,Bodogai M,Martindale JL,Pandey PR,Yang X,Biragyn A,Abdelmohsen K,Gorospe M

更新日期：2018-07-01 00:00:00

abstract：:Activating JAK2 point mutations are implicated in the pathogenesis of myeloid and lymphoid malignancies, including high-risk B-cell acute lymphoblastic leukemia (B-ALL). In preclinical studies, treatment of JAK2 mutant leukemias with type I JAK2 inhibitors (e.g., Food and Drug Administration [FDA]-approved ruxolitinib...

journal_title：Genes & development

authors： Kim SK,Knight DA,Jones LR,Vervoort S,Ng AP,Seymour JF,Bradner JE,Waibel M,Kats L,Johnstone RW

更新日期：2018-06-01 00:00:00

abstract：:The identification of telomerase-negative HAATI (heterochromatin amplification-mediated and telomerase-independent) cells, in which telomeres are superseded by nontelomeric heterochromatin tracts, challenged the idea that canonical telomeres are essential for chromosome linearity and raised crucial questions as to how...

journal_title：Genes & development

authors： Begnis M,Apte MS,Masuda H,Jain D,Wheeler DL,Cooper JP

更新日期：2018-04-01 00:00:00

abstract：:Although branchpoint recognition is an essential component of intron excision during the RNA splicing process, the branchpoint itself is frequently assumed to be a basal, rather than regulatory, sequence feature. However, this assumption has not been systematically tested due to the technical difficulty of identifying...

journal_title：Genes & development

authors： Pineda JMB,Bradley RK

更新日期：2018-04-01 00:00:00

abstract：:The p53 tumor suppressor protein is the most well studied as a regulator of transcription in the nucleus, where it exists primarily as a tetramer. However, there are other oligomeric states of p53 that are relevant to its regulation and activities. In unstressed cells, p53 is normally held in check by MDM2 that target...

journal_title：Genes & development

authors： Katz C,Low-Calle AM,Choe JH,Laptenko O,Tong D,Joseph-Chowdhury JN,Garofalo F,Zhu Y,Friedler A,Prives C

更新日期：2018-03-01 00:00:00

abstract：:Cis-regulatory modules (CRMs) are defined by unique combinations of transcription factor-binding sites. Emerging evidence suggests that the number, affinity, and organization of sites play important roles in regulating enhancer output and, ultimately, gene expression. Here, we investigate how the cis-regulatory logic ...

journal_title：Genes & development

authors： Boisclair Lachance JF,Webber JL,Hong L,Dinner AR,Rebay I

更新日期：2018-03-01 00:00:00

abstract：:Multiple congenital disorders often present complex phenotypes, but how the mutation of individual genetic factors can lead to multiple defects remains poorly understood. In the present study, we used human neuroepithelial (NE) cells and CHARGE patient-derived cells as an in vitro model system to identify the function...

journal_title：Genes & development

authors： Chai M,Sanosaka T,Okuno H,Zhou Z,Koya I,Banno S,Andoh-Noda T,Tabata Y,Shimamura R,Hayashi T,Ebisawa M,Sasagawa Y,Nikaido I,Okano H,Kohyama J

更新日期：2018-01-15 00:00:00

abstract：:The number of known long noncoding RNA (lncRNA) functions is rapidly growing, but how those functions are encoded in their sequence and structure remains poorly understood. NORAD (noncoding RNA activated by DNA damage) is a recently characterized, abundant, and highly conserved lncRNA that is required for proper mitot...

journal_title：Genes & development

authors： Tichon A,Perry RB,Stojic L,Ulitsky I

更新日期：2018-01-01 00:00:00

abstract：:Chromatin is organized into higher-order structures that form subcompartments in interphase nuclei. Different categories of specialized enzymes act on chromatin and regulate its compaction and biophysical characteristics in response to physiological conditions. We present an overview of the function of chromatin struc...

journal_title：Genes & development

authors： Hauer MH,Gasser SM

更新日期：2017-11-15 00:00:00

abstract：:The molecular mechanisms driving brain development at risk in autism spectrum disorders (ASDs) remain mostly unknown. Previous studies have implicated the transcription factor FOXP1 in both brain development and ASD pathophysiology. However, the specific molecular pathways both upstream of and downstream from FOXP1 ar...

journal_title：Genes & development

authors： Usui N,Araujo DJ,Kulkarni A,Co M,Ellegood J,Harper M,Toriumi K,Lerch JP,Konopka G

更新日期：2017-10-15 00:00:00

abstract：:Disruption of the balanced modulation of reversible tyrosine phosphorylation has been implicated in the etiology of various human cancers, including breast cancer. Protein Tyrosine Phosphatase N23 (PTPN23) resides in chromosomal region 3p21.3, which is hemizygously or homozygously lost in some breast cancer patients. ...

journal_title：Genes & development

authors： Zhang S,Fan G,Hao Y,Hammell M,Wilkinson JE,Tonks NK

更新日期：2017-10-01 00:00:00

abstract：:Maternal imprinting at the Xist gene is essential to achieve paternal allele-specific imprinted X-chromosome inactivation (XCI) in female mammals. However, the mechanism underlying Xist imprinting is unclear. Here we show that the Xist locus is coated with a broad H3K27me3 domain that is established during oocyte grow...

journal_title：Genes & development

authors： Inoue A,Jiang L,Lu F,Zhang Y

更新日期：2017-10-01 00:00:00

abstract：:TP53 is the most frequently mutated gene in human cancer. Many mutant p53 proteins exert oncogenic gain-of-function (GOF) properties that contribute to metastasis, but the mechanisms mediating these functions remain poorly defined in vivo. To elucidate how mutant p53 GOF drives metastasis, we developed a traceable som...

journal_title：Genes & development

authors： Pourebrahim R,Zhang Y,Liu B,Gao R,Xiong S,Lin PP,McArthur MJ,Ostrowski MC,Lozano G

更新日期：2017-09-15 00:00:00

abstract：:Direct reprogramming of fibroblasts to cardiomyocytes represents a potential means of restoring cardiac function following myocardial injury. AKT1 in the presence of four cardiogenic transcription factors, GATA4, HAND2, MEF2C, and TBX5 (AGHMT), efficiently induces the cardiac gene program in mouse embryonic fibroblast...

journal_title：Genes & development

authors： Zhou H,Morales MG,Hashimoto H,Dickson ME,Song K,Ye W,Kim MS,Niederstrasser H,Wang Z,Chen B,Posner BA,Bassel-Duby R,Olson EN

更新日期：2017-09-01 00:00:00