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Nuclear Receptors and Epigenetic Regulation

  • Ornella I. Selmin
  • Alberto PG Romagnolo
  • Donato F. Romagnolo
Living reference work entry

Abstract

The activity of nuclear receptor (NR) at target genes is regulated by the interaction with ligands, coactivators, corepressors, DNA, and histone-modifying proteins. These interactions influence chromatin status and transcription of genes encoding for factors that impinge on breast cancer processes such as cell proliferation, invasion and metastasis, DNA repair, and differentiation. Epigenetic mechanisms such as DNA methylation at CpG islands and histone modifications influence transcriptional activity directed by various NR including the estrogen, progesterone, aromatic hydrocarbon, vitamin D, and retinoic X receptor. In breast tissues, dietary compounds may alter cancer risk through agonistic and antagonistic interactions toward one or more NR. Examples of food ligands for NR include resveratrol, genistein, curcumin, vitamin D, and omega-3 fatty acids. Based on the information that ~80% of breast cancer cases are sporadic, i.e., lack a hereditary origin, studies that focus on the interaction of specific or combinations of food compounds with NR promise to unravel new epigenetic strategies against breast cancer.

Keywords

Dietary ligands Nuclear receptors Epigenetics DNA methylation Histone modification Breast cancer prevention 

List of Abbreviations

1,25(OH)2−D3

Cholecalciferol

5-aza

5-aza-2′-deoxycytidine

AA

Arachidonic acid

ABC1

Amplified in breast cancer 1

AF2

Activation function domain 2

AhR

Aromatic hydrocarbon receptor

AI

Aromatase inhibitor

AP1

Activator protein 1

ARNT

Aromatic hydrocarbon receptor nuclear translocator

BRCA1

Breast cancer 1

CBP

cAMP-response element-binding protein

CCND1

Cyclin D1

CCNE

Cyclin E

CCNG2

Cyclin G2

CDH1

E-cadherin

CDK4

Cyclin-dependent kinase 4

COUP-TFII

Chicken ovalbumin upstream promoter transition factor II

COX2

Cyclooxygenase2

CpG

Cytosine-phosphate-guanine

CR

Caloric restriction

CRE

cAMP-response element

CTSD

Cathepsin D

CYP1A1

Cytochrome P450, family 1, subfamily A, polypeptide 1

CYP1B1

Cytochrome P450, family 1, subfamily B, polypeptide 1

CYP24A1

Cytochrome P450, family 24, subfamily A, polypeptide 1

CYP27B1

Cytochrome P450, family 27, subfamily B, polypeptide 1

DHA

Docosahexaenoic acid

DNMT

DNA methyltransferase

EGCG

Epigallocatechin gallate

EHMT1

Eukaryotic histone methyltransferase 1

EPA

Eicosapentaenoic acid

EPHB3

Ephrin type-B receptor 3

ER

Estrogen receptor

ERE

Estrogen receptor element

ERK

Extracellular signal-regulated kinase 1

EVOO

Extra-virgin olive oil

EZH2

Enhancer of zeste homolog 2

FOXO-1

Forkhead box O1

GADD45

Growth arrest and DNA damage 45

GRIP1

Glucocorticoid receptor interacting protein 1

H3K23Ac

Acetylated histone 3 at lysine 23

H3K27me3

Trimethylated histone 3 at lysine 27

H3K4me

Methylated histone 3 at lysine 4

H3K9Ac

Acetylated histone 3 at lysine 9

H3Ser10P

Phosphorylated H3 at serine 10

H4Ac

Acetylated histone 4

H4K20Ac

Acetylated histone 4 at lysine 20

H4K20me3

Trimethylated histone 4 at lysine 20

HAT

Histone acetyltransferase

HDAC

Histone deacetylase

HDM

Histone demethylase

HER2

Human epidermal growth factor receptor 2

HLCS

Holocarboxylase synthetase

HMT

Histone methyltransferase

HP1

Heterochromatin protein 1

IGFBP4

Insulin-like growth factor-binding protein 4

KL

Klotho

LA

Linoleic acid

LCA

Lithocholic acid

LOH

Loss of heterozygosity

LSD1

Lysine demethylase 1

LUM

Luminal

MBD2

Methyl-binding domain protein 2

MeCP2

Methylated cytosine-binding protein 2

MLK3

Mixed lineage kinase 3

MLL3

Mixed lineage leukemia 3

NCoA

Nuclear coactivator

NCoR

Nuclear corepressor

NcRNA

Noncoding RNA

NFkB

Nuclear factor kB

NR

Nuclear receptor

PI3K

Phosphoinositide 3-kinase

PIK3K

Phosphatidylinositol-4,5-bisphosphate 3 kinase

PKA

Protein kinase A

PKCA

Protein kinase C alpha

PolII

RNA polymerase II

PR

Progesterone receptor

PRG

Progesterone receptor gene

PTEN

Phosphatase and tensin homolog

PTGES

Prostaglandin E synthase

RA

Retinoic acid

RAR

Retinoic acid receptor

RARE

Retinoic acid responsive element

RXR

Retinoic X receptor

SET 7/9

Methylase histone-lysine N-methyltransferase SET domain 7/9

SFN

Sulforaphane

Sin3A

Sin 3 member A

SIRT1

Sirtuin 1

SMRT

Silencing-mediator for retinoic and thyroid

SMYD2

SET and MYND domain-containing 2

Sp1

Specificity protein 1

SRC1

Steroid receptor coactivator 1

STAT3

Signal transducer and activator of transcription 3

SWI/SNF

Switch/sucrose non-fermentable nucleosome factor

TAM

Tamoxifen

TRIM6

Tripartite motif-containing 6

TRβ

Thyroid receptor-β

VDR

Vitamin D receptor

VDRE

VDR-responsive element

WIF1

Wnt inhibitory factor 1

XRE

Xenobiotic response element

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Ornella I. Selmin
    • 1
    • 2
  • Alberto PG Romagnolo
    • 2
  • Donato F. Romagnolo
    • 1
    • 2
  1. 1.Department of Nutritional SciencesUniversity of ArizonaTucsonUSA
  2. 2.University of Arizona Cancer Center, College of MedicineUniversity of ArizonaTucsonUSA

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