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Epigenetic choreography of stem cells: the DNA demethylation episode of development

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Abstract

Reversible DNA methylation is a fundamental epigenetic manipulator of the genomic information in eukaryotes. DNA demethylation plays a very significant role during embryonic development and stands out for its contribution in molecular reconfiguration during cellular differentiation for determining stem cell fate. DNA demethylation arbitrated extensive make-over of the genome via reprogramming in the early embryo results in stem cell plasticity followed by commitment to the principal cell lineages. This article attempts to highlight the sequential phases and hierarchical mode of DNA demethylation events during enactment of the molecular strategy for developmental transition. A comprehensive knowledge regarding the pattern of DNA demethylation during embryogenesis and organogenesis and study of the related lacunae will offer exciting avenues for future biomedical research and stem cell-based regenerative therapy.

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Abbreviations

5meC:

5 Methylcytosine

ABL1:

c-abl oncogene 1

AID:

Activation-induced deaminase

AML:

Acute myelogenous leukemia

APOBEC:

Apolipoprotein B mRNA editing enzyme catalytic polypeptide

ARL4C:

ADP-ribosylation factor-like 4C

ASCL1:

Achaete-scute complex homologue 1

AZA:

5-Aza-2′-deoxycytidine

BDNF:

Brain-derived neurotrophic factor

BER:

Base excision repair glycosylases

BGLAP:

Bone gamma-carboxyglutamate (Gla) protein

BMP2:

Bone morphogenetic protein 2

BMP4:

Bone morphogenetic protein 4

CALC-α:

Calcitonin-related polypeptide alpha

CDKN2B:

Cyclin-dependent kinase inhibitor 2B

CEBP-α:

CCAAT/enhancer-binding protein alpha

CHAD:

Chondroadherin

CHK2:

Checkpoint kinase 2

CHM1:

Chondromodulin-I

CLPs:

Common lymphoid progenitors

CML:

Chronic myelomonocytic leukemia

CMPs:

Common myeloid progenitors

CNS:

Central nervous system

CNTF:

Ciliary neurotrophic factor

Col10a1:

α1(X) collagen

Col2a1:

α1 (II) collagen

CT1:

Cardiotrophin-1

CTLA4:

Cytotoxic T-lymphocyte-associated protein

CTNNA1:

Catenin (cadherin-associated protein), Alpha 1

CXCR2:

Chemokine (C-X-C Motif) receptor 2

DACH1:

Dachshund homolog 1

DAZL:

Deleted in azoospermia-like

DC-SIGN:

Dendritic cell-specific ICAM-3 grabbing non-integrin

DMD:

Duchenne muscular dystrophy

DNMT1:

DNA methyltransferase 1

E-CAD:

E-cadherin

EGCs:

Embryonic germ cells

ELF5:

E-74-like factor 5

ELP3:

Elongator complex protein 3

ESCs:

Embryonic stem cells

FABP4:

Fatty acid-binding protein 4

FGF2:

Fibroblast growth factors

FGFR3:

Fibroblast growth factor receptor-3

GADD45A:

Growth arrest and DNA damage-inducible protein 45α

GCNT2:

Glucosaminyl (N-acetyl) transferase 2; I-branching enzyme (I Blood Group)

GFAP:

Glial fibrillary acidic protein

GLUT4:

Glucose transporter type 4

GMPs:

Granulocyte/macrophage progenitors

GP6/GP VI:

Platelet glycoprotein 6/VI

HSCs:

Hematopoietic stem cells

ICM:

Inner cell mass

IFN-γ:

Interferon-gamma

IL-13:

Interleukin 13

IL-17:

Interleukin 17A

IL-1β:

Interleukin-1β

IL-2:

Interleukin 2

IL-4:

Interleukin 4

IL-6:

Interleukin-6

iPSCs:

Induced pluripotent stem cells

iTreg :

Induced regulatory T

JAK–STAT:

Janus Kinase-signal transducer and activator of transcription

JDP2:

Jun dimerization protein 2

JMML:

Juvenile myelomonocytic leukemia

LAG3:

Lymphocyte-activation gene 3

LEP:

Leptin

LIF:

Leukemia inhibitory factor

LPL:

Lipoprotein lipase

MATH3:

Mammalian atonal homologue 3

MBD2b:

Methyl-binding domain protein 2b

MBD4:

Methyl-binding domain protein 4

MDS:

Myelodysplastic syndromes

MEPs:

Megakaryocyte/erythroid progenitors

MGMT:

O6-methylguanine-DNA methyltransferase

MHC II:

Major histocompatibility complex, class II

MPO:

Myeloperoxidase

MRFs:

Myogenic regulatory factors

MSCs:

Mesenchymal stem cells

MYF-5:

Myogenic factor 5

MYOD:

Myogenic differentiation

MYOG:

Myogenin

NEUROG2:

Neurogenin 2

NK:

Natural killer

NKG2A:

NK cell receptor A, also known as KLRC1 (C-type lectin-like inhibitory receptor)

NR4A2:

Nuclear receptor subfamily 4, group A, member 2

NRG:

Neuregulins

NSCs:

Neural stem cells

OC:

Osteocalcin

OCT4:

Octamer-binding transcription factor 4

OPCs:

Oligodendrocyte progenitor cells

OPN:

Osteopontin

OSX:

Osterix

PAX3:

Paired box 3

PAX5:

Paired box protein 5

PCD1:

Programmed cell death 1

PDGF:

Platelet-derived growth factors

PGCs:

Primordial germ cells

PI-PLC beta1:

Phosphoinositide-phospholipase C beta1

PPARγ and PPARγ2:

Peroxisome proliferator-activated receptor-gamma

PRF1:

Perforin 1

PU1:

Purine box factor 1

RAR-β:

Retinoic acid receptor beta

ROR-γt:

Retinoic-acid-receptor-related orphan receptor-γt, or RORC

RUNX1:

Runt-related transcription factor 1

RUNX2:

Runt-related transcription factor 2

SOX2:

SRY box-containing factor 2

SOX9:

SRY (sex determining region Y) box 9

SYCP3:

Synaptonemal complex protein 3

TBX21:

Transcription factor T-Box 21, or T-bet

TDG:

Thymine DNA glycosylase

TE:

Trophectoderm

TET:

Ten-eleven translocation proteins

TH :

T helper

TIM3:

T-cell immunoglobulin mucin 3

TNK:

T cell and natural killer cell

VASN:

Vasorin

WT1:

Wilms tumor 1

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Acknowledgments

S. Kar, A. Shilpi, D. Sengupta, M. Deb, and S. K. Rath are thankful to NIT-Rourkela for granting them fellowships under the Institute Research Scheme. S. Parbin is thankful to DST, government of India for an INSPIRE fellowship. M. Rakshit is thankful to NIT-Rourkela for granting her a postdoctoral research associate position with institute fellowship. We thankfully acknowledge the suggestions and critics of the anonymous reviewer on the original manuscript.

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The authors declare that they do not have any conflict of interest to report.

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Authors and Affiliations

  1. Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, 769008, India

    Swayamsiddha Kar, Sabnam Parbin, Moonmoon Deb, Arunima Shilpi, Dipta Sengupta, Sandip Kumar Rath, Madhumita Rakshit & Samir Kumar Patra

  2. Additional Block Animal Health Centre, Veterinary Office, Oodlabari, Malbazar, Jalpaiguri, West Bengal, India

    Aditi Patra

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  1. Swayamsiddha Kar
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  2. Sabnam Parbin
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  3. Moonmoon Deb
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  9. Samir Kumar Patra
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Correspondence to Samir Kumar Patra.

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Kar, S., Parbin, S., Deb, M. et al. Epigenetic choreography of stem cells: the DNA demethylation episode of development. Cell. Mol. Life Sci. 71, 1017–1032 (2014). https://doi.org/10.1007/s00018-013-1482-2

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  • DOI: https://doi.org/10.1007/s00018-013-1482-2

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