#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Epigenetic Regulation of Cell Type–Specific Expression Patterns in the Human Mammary Epithelium


Differentiation is an epigenetic program that involves the gradual loss of pluripotency and acquisition of cell type–specific features. Understanding these processes requires genome-wide analysis of epigenetic and gene expression profiles, which have been challenging in primary tissue samples due to limited numbers of cells available. Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, as well as gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type–specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation.


Vyšlo v časopise: Epigenetic Regulation of Cell Type–Specific Expression Patterns in the Human Mammary Epithelium. PLoS Genet 7(4): e32767. doi:10.1371/journal.pgen.1001369
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001369

Souhrn

Differentiation is an epigenetic program that involves the gradual loss of pluripotency and acquisition of cell type–specific features. Understanding these processes requires genome-wide analysis of epigenetic and gene expression profiles, which have been challenging in primary tissue samples due to limited numbers of cells available. Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, as well as gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type–specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation.


Zdroje

1. GrafT

EnverT

2009 Forcing cells to change lineages. Nature 462 587 594

2. ListerR

PelizzolaM

DowenRH

HawkinsRD

HonG

2009 Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462 315 322

3. BernsteinBE

MikkelsenTS

XieX

KamalM

HuebertDJ

2006 A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125 315 326

4. KuM

KocheRP

RheinbayE

MendenhallEM

EndohM

2008 Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genet 4 e1000242 doi:10.1371/journal.pgen.1000242

5. StinglJ

RaoufA

EmermanJT

EavesCJ

2005 Epithelial progenitors in the normal human mammary gland. J Mammary Gland Biol Neoplasia 10 49 59

6. ClarkeRB

SpenceK

AndersonE

HowellA

OkanoH

2005 A putative human breast stem cell population is enriched for steroid receptor-positive cells. Dev Biol 277 443 456

7. GudjonssonT

VilladsenR

NielsenHL

Ronnov-JessenL

BissellMJ

2002 Isolation, immortalization, and characterization of a human breast epithelial cell line with stem cell properties. Genes Dev 16 693 706

8. DontuG

AbdallahWM

FoleyJM

JacksonKW

ClarkeMF

2003 In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17 1253 1270

9. AlviAJ

ClaytonH

JoshiC

EnverT

AshworthA

2003 Functional and molecular characterisation of mammary side population cells. Breast Cancer Res 5 R1 8

10. ClaytonH

TitleyI

VivancoM

2004 Growth and differentiation of progenitor/stem cells derived from the human mammary gland. Exp Cell Res 297 444 460

11. RaoufA

ZhaoY

ToK

StinglJ

DelaneyA

2008 Transcriptome analysis of the normal human mammary cell commitment and differentiation process. Cell Stem Cell 3 109 118

12. EirewP

StinglJ

RaoufA

TurashviliG

AparicioS

2008 A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability. Nat Med 14 1384 1389

13. GinestierC

HurMH

Charafe-JauffretE

MonvilleF

DutcherJ

2007 ALDH1 Is a Marker of Normal and Malignant Human Mammary Stem Cells and a Predictor of Poor Clinical Outcome. Cell Stem Cell 1 555 567

14. ManiSA

GuoW

LiaoMJ

EatonEN

AyyananA

2008 The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133 704 715

15. LiuS

DontuG

MantleID

PatelS

AhnNS

2006 Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res 66 6063 6071

16. ShipitsinM

CampbellLL

ArganiP

WeremowiczS

Bloushtain-QimronN

2007 Molecular definition of breast tumor heterogeneity. Cancer Cell 11 259 273

17. Bloushtain-QimronN

YaoJ

SnyderEL

ShipitsinM

CampbellLL

2008 Cell type–specific DNA methylation patterns in the human breast. Proc Natl Acad Sci U S A 105 14076 14081

18. LimE

VaillantF

WuD

ForrestNC

PalB

2009 Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med 15 907 913

19. MeissnerA

MikkelsenTS

GuH

WernigM

HannaJ

2008 Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454 766 770

20. MikkelsenTS

KuM

JaffeDB

IssacB

LiebermanE

2007 Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448 553 560

21. ParkPJ

2009 ChIP-seq: advantages and challenges of a maturing technology. Nat Rev Genet 10 669 680

22. HuM

YaoJ

CaiL

BachmanKE

van den BruleF

2005 Distinct epigenetic changes in the stromal cells of breast cancers. Nat Genet 37 899 905

23. VelculescuVE

ZhangL

VogelsteinB

KinzlerKW

1995 Serial analysis of gene expression. Science 270 484 487

24. Ramalho-SantosM

YoonS

MatsuzakiY

MulliganRC

MeltonDA

2002 “temness” transcriptional profiling of embryonic and adult stem cells. Science 298 597 600

25. KatohM

2010 Network of WNT and Other Regulatory Signaling Cascades in Pluripotent Stem Cells and Cancer Stem Cells. Curr Pharm Biotechnol

26. Kouros-MehrH

SlorachEM

SternlichtMD

WerbZ

2006 GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland. Cell 127 1041 1055

27. Asselin-LabatML

SutherlandKD

BarkerH

ThomasR

ShackletonM

2007 Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation. Nat Cell Biol 9 201 209

28. ZangC

SchonesDE

ZengC

CuiK

ZhaoK

2009 A clustering approach for identification of enriched domains from histone modification ChIP-Seq data. Bioinformatics 25 1952 1958

29. NikolskyY

KirillovE

ZuevR

RakhmatulinE

NikolskayaT

2009 Functional analysis of OMICs data and small molecule compounds in an integrated “nowledge-based”platform. Methods Mol Biol 563 177 196

30. LupienM

EeckhouteJ

MeyerCA

WangQ

ZhangY

2008 FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription. Cell 132 958 970

31. SanzLA

ChamberlainS

SabourinJC

HenckelA

MagnusonT

2008 A mono-allelic bivalent chromatin domain controls tissue-specific imprinting at Grb10. Embo J 27 2523 2532

32. RodriguezJ

MunozM

VivesL

FrangouCG

GroudineM

2008 Bivalent domains enforce transcriptional memory of DNA methylated genes in cancer cells. Proc Natl Acad Sci U S A 105 19809 19814

33. HannaJH

SahaK

JaenischR

2010 Pluripotency and cellular reprogramming: facts, hypotheses, unresolved issues. Cell 143 508 525

34. ZhangX

YazakiJ

SundaresanA

CokusS

ChanSW

2006 Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis. Cell 126 1189 1201

35. JonesPA

1999 The DNA methylation paradox. Trends Genet 15 34 37

36. PolyakK

WeinbergRA

2009 Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 9 265 273

37. MohnF

WeberM

RebhanM

RoloffTC

RichterJ

2008 Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. Mol Cell 30 755 766

38. AkkersRC

van HeeringenSJ

JacobiUG

Janssen-MegensEM

FrancoijsKJ

2009 A hierarchy of H3K4me3 and H3K27me3 acquisition in spatial gene regulation in Xenopus embryos. Dev Cell 17 425 434

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2011 Číslo 4
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#