Evidence map›Paper›PMID 27856528›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2017

In Vivo Hepatic Enhancer Elements in the Human ABCG2 Locus.

Rachel J Eclov, Mee J Kim, Robin P Smith, Xiaomin Liang, Nadav Ahituv, Deanna L Kroetz

Open access · bronzeAbstract read
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. The Evolving Landscape of Gout in the Female: A Narrative Review.Gout, urate, and crystal deposition disease · 2023
    Article
  2. Rare Variants in theDrug metabolism and disposition: the biological fate of chemicals · 2018
    Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Rachel J EclovDepartment of Bioengineering and Therapeutic Sciences (R.J.E., M.J.K., R.P.S., X.L., N.A., D.L.K.); and Institute for Human Genetics (M.J.K., R.P.S., N.A., D.L.K.), University of California, San Francisco, San Francisco, California.
Mee J KimDepartment of Bioengineering and Therapeutic Sciences (R.J.E., M.J.K., R.P.S., X.L., N.A., D.L.K.); and Institute for Human Genetics (M.J.K., R.P.S., N.A., D.L.K.), University of California, San Francisco, San Francisco, California.
Robin P SmithDepartment of Bioengineering and Therapeutic Sciences (R.J.E., M.J.K., R.P.S., X.L., N.A., D.L.K.); and Institute for Human Genetics (M.J.K., R.P.S., N.A., D.L.K.), University of California, San Francisco, San Francisco, California.
Xiaomin LiangDepartment of Bioengineering and Therapeutic Sciences (R.J.E., M.J.K., R.P.S., X.L., N.A., D.L.K.); and Institute for Human Genetics (M.J.K., R.P.S., N.A., D.L.K.), University of California, San Francisco, San Francisco, California.
Nadav AhituvDepartment of Bioengineering and Therapeutic Sciences (R.J.E., M.J.K., R.P.S., X.L., N.A., D.L.K.); and Institute for Human Genetics (M.J.K., R.P.S., N.A., D.L.K.), University of California, San Francisco, San Francisco, California.
Deanna L KroetzDepartment of Bioengineering and Therapeutic Sciences (R.J.E., M.J.K., R.P.S., X.L., N.A., D.L.K.); and Institute for Human Genetics (M.J.K., R.P.S., N.A., D.L.K.), University of California, San Francisco, San Francisco, California deanna.kroetz@ucsf.edu.
University of California, San Francisco · USNorwegian Womens Public Health Association · NO

Funding

UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer Y. Chen · 1986 to 2026
$30.7M
PHARMACOGENETICS OF MEMBRANE TRANSPORTERSU01GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GIACOMINI, KATHLEEN M · 2000 to 2009
$29.2M
Pharmacogenomics of Membrane TransportersU19GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YEE, SOOK WAH · 2010 to 2014
$16.3M
UCSF Nutrition Obesity Research CenterP30DK098722 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHRISTIAN VAISSE · 2015 to 2026
$14.6M
PHARMACEUTICAL SCIENCES AND PHARMACOGENOMICST32GM007175 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, KROETZ, DEANNA L · 1985 to 2021
$7.1M
Characterization of regulatory elements leading to human limb malformationsR01HD059862 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, BEJERANO, GILL · 2009 to 2013
$2.2M
Massively parallel, in vivo functional testing of regulatory elementsR01HG006768 · NHGRI · UNIVERSITY OF WASHINGTON · PI AHITUV, NADAV, SHENDURE, JAY ASHOK · 2012 to 2014
$1.8M
Computational & Functional Annotation of the Zebrafish Genome Regulatory ToolboxR01HG005058 · NHGRI · STANFORD UNIVERSITY · PI AHITUV, NADAV, BEJERANO, GILL · 2009 to 2012
$1.6M
Identification & functional characterization of SIM1 obesity-associated variantsR01DK090382 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, VAISSE, CHRISTIAN · 2012 to 2015
$1.3M
Characterization of neuronal gene regulatory elements associated with epilepsyR01NS079231 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV · 2012 to 2015
$1.2M
NHGRI NIH HHS R01 HG005058NHGRI NIH HHS R01 HG006768NICHD NIH HHS R01 HD059862NIDDK NIH HHS P30 DK026743NIDDK NIH HHS P30 DK098722NIDDK NIH HHS R01 DK090382NIGMS NIH HHS T32 GM007175NIGMS NIH HHS U01 GM061390NIGMS NIH HHS U19 GM061390NINDS NIH HHS R01 NS079231
6 · The paper itself

Abstract

ABCG2 encodes the mitoxantrone resistance protein (MXR; breast cancer resistance protein), an ATP-binding cassette (ABC) efflux membrane transporter. Computational analysis of the ∼300 kb region of DNA surrounding ABCG2 (chr4:88911376-89220011, hg19) identified 30 regions with potential cis-regulatory capabilities. These putative regulatory regions were tested for their enhancer and suppressor activity in a human liver cell line using luciferase reporter assays. The in vitro enhancer and suppressor assays identified four regions that decreased gene expression and five regions that increased expression >1.6-fold. Four of five human hepatic in vitro enhancers were confirmed as in vivo liver enhancers using the mouse hydrodynamic tail vein injection assay. Two of the in vivo liver enhancers (ABCG2RE1 and ABCG2RE9) responded to 17β-estradiol or rifampin in human cell lines, and ABCG2RE9 had ChIP-seq evidence to support the binding of several transcription factors and the transcriptional coactivator p300 in human hepatocytes. This study identified genomic regions surrounding human ABCG2 that can function as regulatory elements, some with the capacity to alter gene expression upon environmental stimulus. The results from this research will drive future investigations of interindividual variation in ABCG2 expression and function that contribute to differences in drug response.

Indexed as

Enhancer Elements, GeneticAnimalsAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily G, Member 2Cloning, MolecularDrug Resistance, NeoplasmEstradiolHCT116 CellsHEK293 CellsHepatocytesHep G2 CellsHumansLiverLuciferases, RenillaMCF-7 CellsMiceAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily G, Member 2EstradiolLuciferases, RenillaMitoxantroneRifampin

Identifiers

PMID27856528
PMCPMC5267518
OpenAlexW2553834167

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.