Genome-wide landscape of liver X receptor chromatin binding and gene regulation in human macrophagesReport as inadecuate




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BMC Genomics

, 13:50

Human and rodent genomic

Abstract

BackgroundThe liver X receptors LXRs are oxysterol sensing nuclear receptors with multiple effects on metabolism and immune cells. However, the complete genome-wide cistrome of LXR in cells of human origin has not yet been provided.

ResultsWe performed ChIP-seq in phorbol myristate acetate-differentiated THP-1 cells macrophage-type after stimulation with the potent synthetic LXR ligand T0901317 T09. Microarray gene expression analysis was performed in the same cellular model. We identified 1357 genome-wide LXR locations FDR < 1%, of which 526 were observed after T09 treatment. De novo analysis of LXR binding sequences identified a DR4-type element as the major motif. On mRNA level T09 up-regulated 1258 genes and repressed 455 genes. Our results show that LXR actions are focused on 112 genomic regions that contain up to 11 T09 target genes per region under the control of highly stringent LXR binding sites with individual constellations for each region. We could confirm that LXR controls lipid metabolism and transport and observed a strong association with apoptosis-related functions.

ConclusionsThis first report on genome-wide binding of LXR in a human cell line provides new insights into the transcriptional network of LXR and its target genes with their link to physiological processes, such as apoptosis.

The gene expression microarray and sequence data have been submitted collectively to the NCBI Gene Expression Omnibus http:-www.ncbi.nlm.nih.gov-geo under accession number GSE28319.

AbbreviationsABCATP-binding cassette transporter

ACLS3acyl-CoA synthetase long-chain family member 3

ADMadrenomedullin

ChIPchromatin immunoprecipitation

CNNM4cyclin M4

DEdifferentially expressed

DMSOdimethyl sulfoxide

DR4direct repeat spaced by 4 nucleotides

EGR1early growth response protein

EReverted repeat

ETF1eukaryotic translation termination factor 1

EWSR1Ewing sarcoma breakpoint region 1

FDRfalse discovery rate

FLI1friend leukemia virus integration 1

FEfold enrichment

GPR137G protein-coupled receptor 137

GOgene ontology

GWGW3965

HARShistidyl-tRNA synthetase

IgGimmunoglobulin gamma

IRinverted repeat

KLF4krüppel-like factor 4

LXRliver X receptor

MYFmyogenic factor

MYLIPmyosin regulatory light chain interact

NACAnascent polypeptide-associated complex alpha subunit

NR1H3LXRα

PMAphorbol myristate acetate

PPARperoxisome proliferator-activated receptor

PRDX5peroxiredoxin 5, PRIM1, primase, DNA, polypeptide 1

PTGES3prostaglandin E synthase 3

PUF60poly-U binding splicing factor 60 KDa

PWMposition weight matrix

qPCRquantitative real-time PCR

REresponse element

RPLP0ribosomal protein large P0

RREB1Ras-responsive element-binding protein 1

RSATregulatory sequence analysis tools

RXRretinoid X receptor

SCDstearoyl-CoA desaturase

SCL3A2solute carrier family 3A2

SMPDL3Asphingomyelin phosphodiesterase: acid-like 3A

SP1Sp1 transcription factor

SPIBSpi-B transcription factor

T09T0901317

TATDN2TatD DNase domain containing 2

TRMT112tRNA methyltransferase 11-2 homolog

TSStranscription start site

VDRvitamin D receptor.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-13-50 contains supplementary material, which is available to authorized users.

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Author: Petri Pehkonen - Lynn Welter-Stahl - Janine Diwo - Jussi Ryynänen - Anke Wienecke-Baldacchino - Sami Heikkinen - Eckardt T

Source: https://link.springer.com/article/10.1186/1471-2164-13-50







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