当前位置： SCI文献检索 > AMERICAN JOURNAL OF HUMAN GENETICS期刊下所有文献 > cis Elements that Mediate RNA Polymerase II Pausing Regulate Human Gene Expression.

cis Elements that Mediate RNA Polymerase II Pausing Regulate Human Gene Expression.

Abstract：

:Aberrant gene expression underlies many human diseases. RNA polymerase II (Pol II) pausing is a key regulatory step in transcription. Here, we mapped the locations of RNA Pol II in normal human cells and found that RNA Pol II pauses in a consistent manner across individuals and cell types. At more than 1,000 genes including MYO1E and SESN2, RNA Pol II pauses at precise nucleotide locations. Characterization of these sites shows that RNA Pol II pauses at GC-rich regions that are marked by a sequence motif. Sixty-five percent of the pause sites are cytosines. By differential allelic gene expression analysis, we showed in our samples and a population dataset from the Genotype-Tissue Expression (GTEx) consortium that genes with more paused polymerase have lower expression levels. Furthermore, mutagenesis of the pause sites led to a significant increase in promoter activities. Thus, our data uncover that RNA Pol II pauses precisely at sites with distinct sequence features that in turn regulate gene expression.

journal_name

Am J Hum Genet

journal_title

American journal of human genetics

authors

Watts JA,Burdick J,Daigneault J,Zhu Z,Grunseich C,Bruzel A,Cheung VG

doi

10.1016/j.ajhg.2019.08.003

subject

Has Abstract

pub_date

2019-10-03 00:00:00

pages

677-688

issue

4

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(19)30306-4

journal_volume

105

pub_type

杂志文章

相关文献

AMERICAN JOURNAL OF HUMAN GENETICS文献大全
  • Mapping a Mendelian form of intracranial aneurysm to 1p34.3-p36.13.

    abstract：:The identification of pathways that underlie common disease has been greatly impacted by the study of rare families that segregate single genes with large effect. Intracranial aneurysm is a common neurological problem; the rupture of these aneurysms constitutes a frequently catastrophic neurologic event. The pathogene...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/426953

    authors： Nahed BV,Seker A,Guclu B,Ozturk AK,Finberg K,Hawkins AA,DiLuna ML,State M,Lifton RP,Gunel M

    更新日期：2005-01-01 00:00:00

  • Genome-wide comparison of African-ancestry populations from CARe and other cohorts reveals signals of natural selection.

    abstract：:The study of recent natural selection in human populations has important applications to human history and medicine. Positive natural selection drives the increase in beneficial alleles and plays a role in explaining diversity across human populations. By discovering traits subject to positive selection, we can better...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2011.07.025

    authors： Bhatia G,Patterson N,Pasaniuc B,Zaitlen N,Genovese G,Pollack S,Mallick S,Myers S,Tandon A,Spencer C,Palmer CD,Adeyemo AA,Akylbekova EL,Cupples LA,Divers J,Fornage M,Kao WH,Lange L,Li M,Musani S,Mychaleckyj JC,Og

    更新日期：2011-09-09 00:00:00

  • Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11.

    abstract：:Rupture of intracranial aneurysms (IAs) causes subarachnoid hemorrhage, a devastating condition with high morbidity and mortality. Angiographic and autopsy studies show that IA is a common disorder, with a prevalence of 3%-6%. Although IA has a substantial genetic component, little attention has been given to the gene...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/323614

    authors： Onda H,Kasuya H,Yoneyama T,Takakura K,Hori T,Takeda J,Nakajima T,Inoue I

    更新日期：2001-10-01 00:00:00

  • Effect of reproductive compensation and the desire to have male offspring on the incidence of a sex-linked lethal disease.

    abstract：:The effects of reproductive compensation on an X-linked recessive lethal are examined. Complete compensation without regard to the sex of the offspring increases the incidence of female carriers by a factor of 1.5, and of affected males by 1.33. However, if families reproduce until they have a healthy male offspring, ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Templeton AR,Yokoyama S

    更新日期：1980-07-01 00:00:00

  • A novel class of Pseudoautosomal region 1 deletions downstream of SHOX is associated with Leri-Weill dyschondrosteosis.

    abstract：:Leri-Weill dyschondrosteosis (LWD) is a pseudoautosomal dominant disorder characterized by disproportionate short stature and a characteristic curving of the radius, known as the "Madelung deformity." SHOX mutations resulting in SHOX haploinsufficiency have been found in LWD and in a variable proportion of patients wi...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/449313

    authors： Benito-Sanz S,Thomas NS,Huber C,Gorbenko del Blanco D,Aza-Carmona M,Crolla JA,Maloney V,Rappold G,Argente J,Campos-Barros A,Cormier-Daire V,Heath KE

    更新日期：2005-10-01 00:00:00

  • A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel.

    abstract：:Catecholamine-induced polymorphic ventricular tachycardia (PVT) is characterized by episodes of syncope, seizures, or sudden death, in response to physical activity or emotional stress. Two modes of inheritance have been described: autosomal dominant and autosomal recessive. Mutations in the ryanodine receptor 2 gene ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/324565

    authors： Lahat H,Pras E,Olender T,Avidan N,Ben-Asher E,Man O,Levy-Nissenbaum E,Khoury A,Lorber A,Goldman B,Lancet D,Eldar M

    更新日期：2001-12-01 00:00:00

  • A genomewide screen for late-onset Alzheimer disease in a genetically isolated Dutch population.

    abstract：:Alzheimer disease (AD) is the most common cause of dementia. We conducted a genome screen of 103 patients with late-onset AD who were ascertained as part of the Genetic Research in Isolated Populations (GRIP) program that is conducted in a recently isolated population from the southwestern area of The Netherlands. All...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/518720

    authors： Liu F,Arias-Vásquez A,Sleegers K,Aulchenko YS,Kayser M,Sanchez-Juan P,Feng BJ,Bertoli-Avella AM,van Swieten J,Axenovich TI,Heutink P,van Broeckhoven C,Oostra BA,van Duijn CM

    更新日期：2007-07-01 00:00:00

  • De Novo SOX6 Variants Cause a Neurodevelopmental Syndrome Associated with ADHD, Craniosynostosis, and Osteochondromas.

    abstract：:SOX6 belongs to a family of 20 SRY-related HMG-box-containing (SOX) genes that encode transcription factors controlling cell fate and differentiation in many developmental and adult processes. For SOX6, these processes include, but are not limited to, neurogenesis and skeletogenesis. Variants in half of the SOX genes ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2020.04.015

    authors： Tolchin D,Yeager JP,Prasad P,Dorrani N,Russi AS,Martinez-Agosto JA,Haseeb A,Angelozzi M,Santen GWE,Ruivenkamp C,Mercimek-Andrews S,Depienne C,Kuechler A,Mikat B,Ludecke HJ,Bilan F,Le Guyader G,Gilbert-Dussardier B,Ker

    更新日期：2020-06-04 00:00:00

  • Mutations in HPSE2 cause urofacial syndrome.

    abstract：:Urinary voiding dysfunction in childhood, manifesting as incontinence, dysuria, and urinary frequency, is a common condition. Urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2010.05.006

    authors： Daly SB,Urquhart JE,Hilton E,McKenzie EA,Kammerer RA,Lewis M,Kerr B,Stuart H,Donnai D,Long DA,Burgu B,Aydogdu O,Derbent M,Garcia-Minaur S,Reardon W,Gener B,Shalev S,Smith R,Woolf AS,Black GC,Newman WG

    更新日期：2010-06-11 00:00:00

  • Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility.

    abstract：:We recently reported that a sequence variant in the cell-cycle-checkpoint kinase CHEK2 (CHEK2 1100delC) is a low-penetrance breast cancer-susceptibility allele in noncarriers of BRCA1 or BRCA2 mutations. To investigate whether other CHEK2 variants confer susceptibility to breast cancer, we screened the full CHEK2 codi...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/373965

    authors： Schutte M,Seal S,Barfoot R,Meijers-Heijboer H,Wasielewski M,Evans DG,Eccles D,Meijers C,Lohman F,Klijn J,van den Ouweland A,Futreal PA,Nathanson KL,Weber BL,Easton DF,Stratton MR,Rahman N,Breast Cancer Linkage Consortiu

    更新日期：2003-04-01 00:00:00

  • Translocation involving 1p and 17q is a recurrent genetic alteration of human neuroblastoma cells.

    abstract：:Human neuroblastoma cells often are monosomic for the distal portion of 1p (1p36). We report that the deleted 1p material in cells of neuroblastoma lines is preferentially replaced by material from chromosome 17, resulting from an unbalanced 1;17 translocation. Chromosome 17 often acquires instability, followed by the...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Savelyeva L,Corvi R,Schwab M

    更新日期：1994-08-01 00:00:00

  • Mental retardation in heterozygotes for the fragile-X mutation: evidence in favor of an X inactivation-dependent effect.

    abstract：:The still debated question of whether the expression of mental retardation in heterozygous carriers of the Martin-Bell syndrome is influenced by X inactivation has been investigated in a group of phase-known double heterozygotes for the FRA-X mutant and the G6PD Mediterranean variant. In these individuals, the number ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Rocchi M,Archidiacono N,Rinaldi A,Filippi G,Bartolucci G,Fancello GS,Siniscalco M

    更新日期：1990-04-01 00:00:00

  • Familial inheritance of a DXS164 deletion mutation from a heterozygous female.

    abstract：:Restriction-fragment-length-polymorphism analysis was used to examine a female who is segregating for Duchenne muscular dystrophy (DMD) and a deletion of the DXS164 region of the X chromosome. The segregating female has no prior family history of DMD, and she has two copies of the DXS164 region in her peripheral blood...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Lanman JT Jr,Pericak-Vance MA,Bartlett RJ,Chen JC,Yamaoka L,Koh J,Speer MC,Hung WY,Roses AD

    更新日期：1987-08-01 00:00:00

  • Meta-analysis of 13 genome scans reveals multiple cleft lip/palate genes with novel loci on 9q21 and 2q32-35.

    abstract：:Isolated or nonsyndromic cleft lip with or without cleft palate (CL/P) is a common birth defect with a complex etiology. A 10-cM genome scan of 388 extended multiplex families with CL/P from seven diverse populations (2,551 genotyped individuals) revealed CL/P genes in six chromosomal regions, including a novel region...

    journal_title：American journal of human genetics

    pub_type： 杂志文章,meta分析

    doi：10.1086/422475

    authors： Marazita ML,Murray JC,Lidral AC,Arcos-Burgos M,Cooper ME,Goldstein T,Maher BS,Daack-Hirsch S,Schultz R,Mansilla MA,Field LL,Liu YE,Prescott N,Malcolm S,Winter R,Ray A,Moreno L,Valencia C,Neiswanger K,Wyszynski DF,

    更新日期：2004-08-01 00:00:00

  • Patterns of maternal transmission in bipolar affective disorder.

    abstract：:The mode of inheritance of bipolar affective disorder (BPAD) appears complex, and non-Mendelian models of inheritance have been postulated. Two non-Mendelian phenomena, genomic imprinting and mitochondrial inheritance, may contribute to the complex inheritance pattern seen in BPAD. Both imprinting and mitochondrial in...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： McMahon FJ,Stine OC,Meyers DA,Simpson SG,DePaulo JR

    更新日期：1995-06-01 00:00:00

  • Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis-deafness syndrome.

    abstract：:Keratitis-ichthyosis-deafness syndrome (KID) is a rare ectodermal dysplasia characterized by vascularizing keratitis, profound sensorineural hearing loss (SNHL), and progressive erythrokeratoderma, a clinical triad that indicates a failure in development and differentiation of multiple stratifying epithelia. Here, we ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/339986

    authors： Richard G,Rouan F,Willoughby CE,Brown N,Chung P,Ryynänen M,Jabs EW,Bale SJ,DiGiovanna JJ,Uitto J,Russell L

    更新日期：2002-05-01 00:00:00

  • The human ryanodine receptor gene: its mapping to 19q13.1, placement in a chromosome 19 linkage group, and exclusion as the gene causing myotonic dystrophy.

    abstract：:The recent cloning of cDNA encoding the Ca++ release channel (ryanodine receptor) of human sarcoplasmic reticulum has enabled us to use somatic cell hybrids to localize the ryanodine receptor gene (RYR) to the proximal long arm of human chromosome 19. Studies with additional hybrids containing deletions or translocati...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： MacKenzie AE,Korneluk RG,Zorzato F,Fujii J,Phillips M,Iles D,Wieringa B,Leblond S,Bailly J,Willard HF

    更新日期：1990-06-01 00:00:00

  • Bi-allelic Pathogenic Variants in TUBGCP2 Cause Microcephaly and Lissencephaly Spectrum Disorders.

    abstract：:Lissencephaly comprises a spectrum of malformations of cortical development. This spectrum includes agyria, pachygyria, and subcortical band heterotopia; each represents anatomical malformations of brain cortical development caused by neuronal migration defects. The molecular etiologies of neuronal migration anomalies...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2019.09.017

    authors： Mitani T,Punetha J,Akalin I,Pehlivan D,Dawidziuk M,Coban Akdemir Z,Yilmaz S,Aslan E,Hunter JV,Hijazi H,Grochowski CM,Jhangiani SN,Karaca E,Fatih JM,Iwanowski P,Gambin T,Wlasienko P,Goszczanska-Ciuchta A,Bekiesinska-Fi

    更新日期：2019-11-07 00:00:00

  • Bayesian mapping of quantitative trait loci for multiple complex traits with the use of variance components.

    abstract：:Complex traits important for humans are often correlated phenotypically and genetically. Joint mapping of quantitative-trait loci (QTLs) for multiple correlated traits plays an important role in unraveling the genetic architecture of complex traits. Compared with single-trait analysis, joint mapping addresses more que...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/519495

    authors： Liu J,Liu Y,Liu X,Deng HW

    更新日期：2007-08-01 00:00:00

  • Population heterogeneity of the Hpa I restriction site associated with the beta globin gene: implications for prenatal diagnosis.

    abstract：:The Hpa I restriction endonuclease site polymorphism that results in some human beta globin genes being contained in a 13-kilobase (kb) DNA restriction fragment rather than in the usual 7.6-kb fragment has been reported to be in linkage disequilibrium with the beta S mutation. The frequency of the 13-kb fragment among...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Panny SR,Scott AF,Smith KD,Phillips JA 3rd,Kazazian HH Jr,Talbot CC Jr,Boehm CD

    更新日期：1981-01-01 00:00:00

  • On Using Local Ancestry to Characterize the Genetic Architecture of Human Traits: Genetic Regulation of Gene Expression in Multiethnic or Admixed Populations.

    abstract：:Understanding the nature of the genetic regulation of gene expression promises to advance our understanding of the genetic basis of disease. However, the methodological impact of the use of local ancestry on high-dimensional omics analyses, including, most prominently, expression quantitative trait loci (eQTL) mapping...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2019.04.009

    authors： Zhong Y,Perera MA,Gamazon ER

    更新日期：2019-06-06 00:00:00

  • OUTRIDER: A Statistical Method for Detecting Aberrantly Expressed Genes in RNA Sequencing Data.

    abstract：:RNA sequencing (RNA-seq) is gaining popularity as a complementary assay to genome sequencing for precisely identifying the molecular causes of rare disorders. A powerful approach is to identify aberrant gene expression levels as potential pathogenic events. However, existing methods for detecting aberrant read counts ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2018.10.025

    authors： Brechtmann F,Mertes C,Matusevičiūtė A,Yépez VA,Avsec Ž,Herzog M,Bader DM,Prokisch H,Gagneur J

    更新日期：2018-12-06 00:00:00

  • Contrasting linkage-disequilibrium patterns between cases and controls as a novel association-mapping method.

    abstract：:Identification and description of genetic variation underlying disease susceptibility, efficacy, and adverse reactions to drugs remains a difficult problem. One of the important steps in the analysis of variation in a candidate region is the characterization of linkage disequilibrium (LD). In a region of genetic assoc...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/503710

    authors： Zaykin DV,Meng Z,Ehm MG

    更新日期：2006-05-01 00:00:00

  • Age trends in human chiasma frequencies and recombination fractions. I. Chiasma frequencies.

    abstract：:Chiasma frequency data on 183 males were subjected to an analysis of covariance. There appeared to be little or no linear trend in chiasma frequency with age. This conclusion was supported by a detailed analysis of chiasma frequencies for each autosome from 21 males. There were, however, significant differences among ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Lange K,Page BM,Elston RC

    更新日期：1975-05-01 00:00:00

  • Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits.

    abstract：:Subcutaneous adipose tissue stores excess lipids and maintains energy balance. We performed expression quantitative trait locus (eQTL) analyses by using abdominal subcutaneous adipose tissue of 770 extensively phenotyped participants of the METSIM study. We identified cis-eQTLs for 12,400 genes at a 1% false-discovery...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2017.01.027

    authors： Civelek M,Wu Y,Pan C,Raulerson CK,Ko A,He A,Tilford C,Saleem NK,Stančáková A,Scott LJ,Fuchsberger C,Stringham HM,Jackson AU,Narisu N,Chines PS,Small KS,Kuusisto J,Parks BW,Pajukanta P,Kirchgessner T,Collins FS,G

    更新日期：2017-03-02 00:00:00

  • Topical enzyme-replacement therapy restores transglutaminase 1 activity and corrects architecture of transglutaminase-1-deficient skin grafts.

    abstract：:Transglutaminase-1 (TG1)-deficient autosomal-recessive congenital ichthyosis (ARCI) is a rare and severe genetic skin disease caused by mutations in TGM1. It is characterized by collodion babies at birth, dramatically increased transepidermal water loss (TEWL), and lifelong pronounced scaling. The disease has a tremen...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2013.08.003

    authors： Aufenvenne K,Larcher F,Hausser I,Duarte B,Oji V,Nikolenko H,Del Rio M,Dathe M,Traupe H

    更新日期：2013-10-03 00:00:00

  • Polymorphism in the 5'-flanking region of the human insulin gene and the incidence of diabetes.

    abstract：:DNA length polymorphism in the 5'-flanking region of the human insulin gene has been reported by Bell et al. (1981), Rotwein et al. (1981), and Owerbach and Nerup (1982). Bgl I digestions of human DNA that have been hybridized to an insulin probe using the Southern technique shows that there are two distinct groups of...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Yokoyama S

    更新日期：1983-03-01 00:00:00

  • Mutations in CAPN1 Cause Autosomal-Recessive Hereditary Spastic Paraplegia.

    abstract：:Hereditary spastic paraplegia (HSP) is a genetically and clinically heterogeneous disease characterized by spasticity and weakness of the lower limbs with or without additional neurological symptoms. Although more than 70 genes and genetic loci have been implicated in HSP, many families remain genetically undiagnosed,...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2016.04.002

    authors： Gan-Or Z,Bouslam N,Birouk N,Lissouba A,Chambers DB,Vérièpe J,Androschuk A,Laurent SB,Rochefort D,Spiegelman D,Dionne-Laporte A,Szuto A,Liao M,Figlewicz DA,Bouhouche A,Benomar A,Yahyaoui M,Ouazzani R,Yoon G,Dupré N,

    更新日期：2016-05-05 00:00:00

  • De novo mutations in the genome organizer CTCF cause intellectual disability.

    abstract：:An increasing number of genes involved in chromatin structure and epigenetic regulation has been implicated in a variety of developmental disorders, often including intellectual disability. By trio exome sequencing and subsequent mutational screening we now identified two de novo frameshift mutations and one de novo m...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2013.05.007

    authors： Gregor A,Oti M,Kouwenhoven EN,Hoyer J,Sticht H,Ekici AB,Kjaergaard S,Rauch A,Stunnenberg HG,Uebe S,Vasileiou G,Reis A,Zhou H,Zweier C

    更新日期：2013-07-11 00:00:00

  • A subset-based approach improves power and interpretation for the combined analysis of genetic association studies of heterogeneous traits.

    abstract：:Pooling genome-wide association studies (GWASs) increases power but also poses methodological challenges because studies are often heterogeneous. For example, combining GWASs of related but distinct traits can provide promising directions for the discovery of loci with small but common pleiotropic effects. Classical a...

    journal_title：American journal of human genetics

    pub_type： 杂志文章,meta分析

    doi：10.1016/j.ajhg.2012.03.015

    authors： Bhattacharjee S,Rajaraman P,Jacobs KB,Wheeler WA,Melin BS,Hartge P,GliomaScan Consortium.,Yeager M,Chung CC,Chanock SJ,Chatterjee N

    更新日期：2012-05-04 00:00:00