p63 establishes epithelial enhancers at critical craniofacial development genes.

Abstract:

:The transcription factor p63 is a key mediator of epidermal development. Point mutations in p63 in patients lead to developmental defects, including orofacial clefting. To date, knowledge on how pivotal the role of p63 is in human craniofacial development is limited. Using an inducible transdifferentiation model, combined with epigenomic sequencing and multicohort meta-analysis of genome-wide association studies data, we show that p63 establishes enhancers at craniofacial development genes to modulate their transcription. Disease-specific substitution mutation in the DNA binding domain or sterile alpha motif protein interaction domain of p63, respectively, eliminates or reduces establishment of these enhancers. We show that enhancers established by p63 are highly enriched for single-nucleotide polymorphisms associated with nonsyndromic cleft lip ± cleft palate (CL/P). These orthogonal approaches indicate a strong molecular link between p63 enhancer function and CL/P, illuminating molecular mechanisms underlying this developmental defect and revealing vital regulatory elements and new candidate causative genes.

journal_name

Sci Adv

journal_title

Science advances

authors

Lin-Shiao E,Lan Y,Welzenbach J,Alexander KA,Zhang Z,Knapp M,Mangold E,Sammons M,Ludwig KU,Berger SL

doi

10.1126/sciadv.aaw0946

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

eaaw0946

issue

5

issn

2375-2548

pii

aaw0946

journal_volume

5

pub_type

杂志文章
  • Mach-Zehnder interferometry using spin- and valley-polarized quantum Hall edge states in graphene.

    abstract::Confined to a two-dimensional plane, electrons in a strong magnetic field travel along the edge in one-dimensional quantum Hall channels that are protected against backscattering. These channels can be used as solid-state analogs of monochromatic beams of light, providing a unique platform for studying electron interf...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1700600

    authors: Wei DS,van der Sar T,Sanchez-Yamagishi JD,Watanabe K,Taniguchi T,Jarillo-Herrero P,Halperin BI,Yacoby A

    更新日期:2017-08-18 00:00:00

  • Near-infrared and visible light dual-mode organic photodetectors.

    abstract::We report a dual-mode organic photodetector (OPD) that has a trilayer visible light absorber/optical spacer/near-infrared (NIR) light absorber configuration. In the presence of NIR light, photocurrent is produced in the NIR light-absorbing layer due to the trap-assisted charge injection at the organic/cathode interfac...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaw8065

    authors: Lan Z,Lei Y,Chan WKE,Chen S,Luo D,Zhu F

    更新日期:2020-01-31 00:00:00

  • Tensile forces drive a reversible fibroblast-to-myofibroblast transition during tissue growth in engineered clefts.

    abstract::Myofibroblasts orchestrate wound healing processes, and if they remain activated, they drive disease progression such as fibrosis and cancer. Besides growth factor signaling, the local extracellular matrix (ECM) and its mechanical properties are central regulators of these processes. It remains unknown whether transfo...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aao4881

    authors: Kollmannsberger P,Bidan CM,Dunlop JWC,Fratzl P,Vogel V

    更新日期:2018-01-17 00:00:00

  • Cellular defense against latent colonization foiled by human cytomegalovirus UL138 protein.

    abstract::Intrinsic immune defenses mediated by restriction factors inhibit productive viral infections. Select viruses rapidly establish latent infections and, with gene expression profiles that imply cell-autonomous intrinsic defenses, may be the most effective immune control measure against latent reservoirs. We illustrate t...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1501164

    authors: Lee SH,Albright ER,Lee JH,Jacobs D,Kalejta RF

    更新日期:2015-11-27 00:00:00

  • Nanophotonic particle simulation and inverse design using artificial neural networks.

    abstract::We propose a method to use artificial neural networks to approximate light scattering by multilayer nanoparticles. We find that the network needs to be trained on only a small sampling of the data to approximate the simulation to high precision. Once the neural network is trained, it can simulate such optical processe...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aar4206

    authors: Peurifoy J,Shen Y,Jing L,Yang Y,Cano-Renteria F,DeLacy BG,Joannopoulos JD,Tegmark M,Soljačić M

    更新日期:2018-06-01 00:00:00

  • Multiplexed oscillations and phase rate coding in the basal forebrain.

    abstract::Complex behaviors demand temporal coordination among functionally distinct brain regions. The basal forebrain's afferent and efferent structure suggests a capacity for mediating this coordination at a large scale. During performance of a spatial orientation task, synaptic activity in this region was dominated by four ...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aar3230

    authors: Tingley D,Alexander AS,Quinn LK,Chiba AA,Nitz D

    更新日期:2018-08-01 00:00:00

  • Identification and prioritization of novel anti-Wolbachia chemotypes from screening a 10,000-compound diversity library.

    abstract::Lymphatic filariasis and onchocerciasis are two important neglected tropical diseases (NTDs) that cause severe disability. Control efforts are hindered by the lack of a safe macrofilaricidal drug. Targeting the Wolbachia bacterial endosymbionts in these parasites with doxycycline leads to a macrofilaricidal outcome, b...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aao1551

    authors: Johnston KL,Cook DAN,Berry NG,David Hong W,Clare RH,Goddard M,Ford L,Nixon GL,O'Neill PM,Ward SA,Taylor MJ

    更新日期:2017-09-27 00:00:00

  • Tunable and laser-reconfigurable 2D heterocrystals obtained by epitaxial stacking of crystallographically incommensurate Bi2Se3 and MoS2 atomic layers.

    abstract::Vertical stacking is widely viewed as a promising approach for designing advanced functionalities using two-dimensional (2D) materials. Combining crystallographically commensurate materials in these 2D stacks has been shown to result in rich new electronic structure, magnetotransport, and optical properties. In this c...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1601741

    authors: Vargas A,Liu F,Lane C,Rubin D,Bilgin I,Hennighausen Z,DeCapua M,Bansil A,Kar S

    更新日期:2017-07-14 00:00:00

  • Wigner solid pinning modes tuned by fractional quantum Hall states of a nearby layer.

    abstract::We studied a bilayer system hosting two-dimensional electron systems (2DESs) in close proximity but isolated from one another by a thin barrier. One 2DES has low electron density and forms a Wigner solid (WS) at high magnetic fields. The other has much higher density and, in the same field, exhibits fractional quantum...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aao2848

    authors: Hatke AT,Deng H,Liu Y,Engel LW,Pfeiffer LN,West KW,Baldwin KW,Shayegan M

    更新日期:2019-03-15 00:00:00

  • Targeting pulmonary tumor microenvironment with CXCR4-inhibiting nanocomplex to enhance anti-PD-L1 immunotherapy.

    abstract::Anti-programmed cell death 1 ligand 1 (PD-L1) therapy is extraordinarily effective in select patients with cancer. However, insufficient lymphocytic infiltration, weak T cell-induced inflammation, and immunosuppressive cell accumulation in the tumor microenvironment (TME) may greatly diminish the efficacy. Here, we re...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaz9240

    authors: Li Z,Wang Y,Shen Y,Qian C,Oupicky D,Sun M

    更新日期:2020-05-15 00:00:00

  • Somatic cell reprogramming-free generation of genetically modified pigs.

    abstract::Genetically modified pigs for biomedical applications have been mainly generated using the somatic cell nuclear transfer technique; however, this approach requires complex micromanipulation techniques and sometimes increases the risks of both prenatal and postnatal death by faulty epigenetic reprogramming of a donor s...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1600803

    authors: Tanihara F,Takemoto T,Kitagawa E,Rao S,Do LT,Onishi A,Yamashita Y,Kosugi C,Suzuki H,Sembon S,Suzuki S,Nakai M,Hashimoto M,Yasue A,Matsuhisa M,Noji S,Fujimura T,Fuchimoto D,Otoi T

    更新日期:2016-09-14 00:00:00

  • Topological transport of sound mediated by spin-redirection geometric phase.

    abstract::When a dynamic system undergoes a cyclic evolution, a geometric phase that depends only on the path traversed in parameter space can arise in addition to the normal dynamical phase. These geometric phases have profound impacts in both quantum and classical physics. In addition to the geometric phase associated with ba...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaq1475

    authors: Wang S,Ma G,Chan CT

    更新日期:2018-02-16 00:00:00

  • Genes for de novo biosynthesis of omega-3 polyunsaturated fatty acids are widespread in animals.

    abstract::Marine ecosystems are responsible for virtually all production of omega-3 (ω3) long-chain polyunsaturated fatty acids (PUFA), which are essential nutrients for vertebrates. Current consensus is that marine microbes account for this production, given their possession of key enzymes including methyl-end (or "ωx") desatu...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aar6849

    authors: Kabeya N,Fonseca MM,Ferrier DEK,Navarro JC,Bay LK,Francis DS,Tocher DR,Castro LFC,Monroig Ó

    更新日期:2018-05-02 00:00:00

  • Label-free surface-sensitive photonic microscopy with high spatial resolution using azimuthal rotation illumination.

    abstract::Surface plasmon resonance microscopy (SPRM) with single-direction illumination is a powerful platform for biomedical imaging because of its wide-field, label-free, and high-surface-sensitivity imaging capabilities. However, two disadvantages prevent wider use of SPRM. The first is its poor spatial resolution that can ...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aav5335

    authors: Kuai Y,Chen J,Tang X,Xiang Y,Lu F,Kuang C,Xu L,Shen W,Cheng J,Gui H,Zou G,Wang P,Ming H,Liu J,Liu X,Lakowicz JR,Zhang D

    更新日期:2019-03-29 00:00:00

  • Footprints preserve terminal Pleistocene hunt? Human-sloth interactions in North America.

    abstract::Predator-prey interactions revealed by vertebrate trace fossils are extremely rare. We present footprint evidence from White Sands National Monument in New Mexico for the association of sloth and human trackways. Geologically, the sloth and human trackways were made contemporaneously, and the sloth trackways show evid...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aar7621

    authors: Bustos D,Jakeway J,Urban TM,Holliday VT,Fenerty B,Raichlen DA,Budka M,Reynolds SC,Allen BD,Love DW,Santucci VL,Odess D,Willey P,McDonald HG,Bennett MR

    更新日期:2018-04-25 00:00:00

  • Ultimate suppression of thermal transport in amorphous silicon nitride by phononic nanostructure.

    abstract::Engineering the thermal conductivity of amorphous materials is highly essential for the thermal management of future electronic devices. Here, we demonstrate the impact of ultrafine nanostructuring on the thermal conductivity reduction of amorphous silicon nitride (a-Si3N4) thin films, in which the thermal transport i...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abc0075

    authors: Tambo N,Liao Y,Zhou C,Ashley EM,Takahashi K,Nealey PF,Naito Y,Shiomi J

    更新日期:2020-09-25 00:00:00

  • Three-dimensional structure of 22 uncultured ssRNA bacteriophages: Flexibility of the coat protein fold and variations in particle shapes.

    abstract::The single-stranded RNA (ssRNA) bacteriophages are among the simplest known viruses with small genomes and exceptionally high mutation rates. The number of ssRNA phage isolates has remained very low, but recent metagenomic studies have uncovered an immense variety of distinct uncultured ssRNA phages. The coat proteins...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abc0023

    authors: Rūmnieks J,Liekniņa I,Kalniņš G,Šišovs M,Akopjana I,Bogans J,Tārs K

    更新日期:2020-09-02 00:00:00

  • FeSe quantum dots for in vivo multiphoton biomedical imaging.

    abstract::An immense demand in biomedical imaging is to develop efficient photoluminescent probes with high biocompatibility and quantum yield, as well as multiphoton absorption performance to improve penetration depth and spatial resolution. Here, iron selenide (FeSe) quantum dots (QDs) are reported to meet these criteria. The...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aay0044

    authors: Kwon J,Jun SW,Choi SI,Mao X,Kim J,Koh EK,Kim YH,Kim SK,Hwang DY,Kim CS,Lee J

    更新日期:2019-12-06 00:00:00

  • Breaking medical data sharing boundaries by using synthesized radiographs.

    abstract::Computer vision (CV) has the potential to change medicine fundamentally. Expert knowledge provided by CV can enhance diagnosis. Unfortunately, existing algorithms often remain below expectations, as databases used for training are usually too small, incomplete, and heterogeneous in quality. Moreover, data protection i...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abb7973

    authors: Han T,Nebelung S,Haarburger C,Horst N,Reinartz S,Merhof D,Kiessling F,Schulz V,Truhn D

    更新日期:2020-12-02 00:00:00

  • Attenuated diphtheria toxin mediates siRNA delivery.

    abstract::Toxins efficiently deliver cargo to cells by binding to cell surface ligands, initiating endocytosis, and escaping the endolysosomal pathway into the cytoplasm. We took advantage of this delivery pathway by conjugating an attenuated diphtheria toxin to siRNA, thereby achieving gene downregulation in patient-derived gl...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaz4848

    authors: Arnold AE,Smith LJ,Beilhartz GL,Bahlmann LC,Jameson E,Melnyk RA,Shoichet MS

    更新日期:2020-05-01 00:00:00

  • Permafrost thawing puts the frozen carbon at risk over the Tibetan Plateau.

    abstract::Soil organic carbon (SOC) stored in permafrost across the high-latitude/altitude Northern Hemisphere represents an important potential carbon source under future warming. Here, we provide a comprehensive investigation on the spatiotemporal dynamics of SOC over the high-altitude Tibetan Plateau (TP), which has received...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaz3513

    authors: Wang T,Yang D,Yang Y,Piao S,Li X,Cheng G,Fu B

    更新日期:2020-05-06 00:00:00

  • Range of motion in the avian wing is strongly associated with flight behavior and body mass.

    abstract::Avian wing shape is highly variable across species but only coarsely associated with flight behavior, performance, and body mass. An underexplored but potentially explanatory feature is the ability of birds to actively change wing shape to meet aerodynamic and behavioral demands. Across 61 species, we found strong ass...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaw6670

    authors: Baliga VB,Szabo I,Altshuler DL

    更新日期:2019-10-23 00:00:00

  • Breakdown of Hooke's law of elasticity at the Mott critical endpoint in an organic conductor.

    abstract::The Mott metal-insulator transition, a paradigm of strong electron-electron correlations, has been considered as a source of intriguing phenomena. Despite its importance for a wide range of materials, fundamental aspects of the transition, such as its universal properties, are still under debate. We report detailed me...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1601646

    authors: Gati E,Garst M,Manna RS,Tutsch U,Wolf B,Bartosch L,Schubert H,Sasaki T,Schlueter JA,Lang M

    更新日期:2016-12-07 00:00:00

  • Probing biophysical sequence constraints within the transmembrane domains of rhodopsin by deep mutational scanning.

    abstract::Membrane proteins must balance the sequence constraints associated with folding and function against the hydrophobicity required for solvation within the bilayer. We recently found the expression and maturation of rhodopsin are limited by the hydrophobicity of its seventh transmembrane domain (TM7), which contains pol...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aay7505

    authors: Penn WD,McKee AG,Kuntz CP,Woods H,Nash V,Gruenhagen TC,Roushar FJ,Chandak M,Hemmerich C,Rusch DB,Meiler J,Schlebach JP

    更新日期:2020-03-04 00:00:00

  • Highly stable hybrid perovskite light-emitting diodes based on Dion-Jacobson structure.

    abstract::Organic-inorganic hybrid halide perovskites are emerging as promising materials for next-generation light-emitting diodes (LEDs). However, the poor stability of these materials has been the main obstacle challenging their application. Here, we performed first-principles calculations, revealing that the molecule dissoc...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaw8072

    authors: Shang Y,Liao Y,Wei Q,Wang Z,Xiang B,Ke Y,Liu W,Ning Z

    更新日期:2019-08-16 00:00:00

  • Insertion and folding pathways of single membrane proteins guided by translocases and insertases.

    abstract::Biogenesis in prokaryotes and eukaryotes requires the insertion of α-helical proteins into cellular membranes for which they use universally conserved cellular machineries. In bacterial inner membranes, insertion is facilitated by YidC insertase and SecYEG translocon working individually or cooperatively. How insertas...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aau6824

    authors: Serdiuk T,Steudle A,Mari SA,Manioglu S,Kaback HR,Kuhn A,Müller DJ

    更新日期:2019-01-30 00:00:00

  • Dense hydroxyl polyethylene glycol dendrimer targets activated glia in multiple CNS disorders.

    abstract::Poor transport of neuropharmaceutics through central nervous system (CNS) barriers limits the development of effective treatments for CNS disorders. We present the facile synthesis of a novel neuroinflammation-targeting polyethylene glycol-based dendrimer (PEGOL-60) using an efficient click chemistry approach. PEGOL-6...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aay8514

    authors: Sharma A,Sharma R,Zhang Z,Liaw K,Kambhampati SP,Porterfield JE,Lin KC,DeRidder LB,Kannan S,Kannan RM

    更新日期:2020-01-22 00:00:00

  • PET, image-guided HDAC inhibition of pediatric diffuse midline glioma improves survival in murine models.

    abstract::Efforts at altering the dismal prognosis of pediatric midline gliomas focus on direct delivery strategies like convection-enhanced delivery (CED), where a cannula is implanted into tumor. Successful CED treatments require confirmation of tumor coverage, dosimetry, and longitudinal in vivo pharmacokinetic monitoring. T...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abb4105

    authors: Tosi U,Kommidi H,Adeuyan O,Guo H,Maachani UB,Chen N,Su T,Zhang G,Pisapia DJ,Dahmane N,Ting R,Souweidane MM

    更新日期:2020-07-24 00:00:00

  • Targeting the scaffolding role of LSD1 (KDM1A) poises acute myeloid leukemia cells for retinoic acid-induced differentiation.

    abstract::The histone demethylase LSD1 is deregulated in several tumors, including leukemias, providing the rationale for the clinical use of LSD1 inhibitors. In acute promyelocytic leukemia (APL), pharmacological doses of retinoic acid (RA) induce differentiation of APL cells, triggering degradation of the PML-RAR oncogene. AP...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aax2746

    authors: Ravasio R,Ceccacci E,Nicosia L,Hosseini A,Rossi PL,Barozzi I,Fornasari L,Zuffo RD,Valente S,Fioravanti R,Mercurio C,Varasi M,Mattevi A,Mai A,Pavesi G,Bonaldi T,Minucci S

    更新日期:2020-04-08 00:00:00

  • Intra- versus intergroup variance in collective behavior.

    abstract::Animal collective motion arises from the intricate interactions between the natural variability among individuals, and the homogenizing effect of the group, working to generate synchronization and maintain coherence. Here, these interactions were studied using marching locust nymphs under controlled laboratory setting...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aav0695

    authors: Knebel D,Ayali A,Guershon M,Ariel G

    更新日期:2019-01-02 00:00:00