A New Isoform of the Histone Demethylase JMJD2A/KDM4A Is Required for Skeletal Muscle Differentiation

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In proliferating myoblasts, muscle specific genes are silenced by epigenetic modifications at their promoters, including histone H3K9 methylation. Derepression of the promoter of the gene encoding the myogenic factor myogenin (Myog) is key for initiation of muscle differentiation. The mechanism of H3K9 demethylation at the Myog promoter is unclear, however. Here, we identify an isoform of the histone demethylase JMJD2A/KDM4A that lacks the N-terminal demethylase domain (ΔN-JMJD2A). The amount of ΔN-JMJD2A increases during differentiation of C2C12 myoblasts into myotubes. Genome-wide expression profiling and exon-specific siRNA knockdown indicate that, in contrast to the full-length protein, ΔN-JMJD2A is necessary for myotube formation and muscle-specific gene expression. Moreover, ΔN-JMJD2A promotes MyoD-induced conversion of NIH3T3 cells into muscle cells. ChIP-on-chip analysis indicates that ΔN-JMJD2A binds to genes mainly involved in transcriptional control and that this binding is linked to gene activation. ΔN-JMJD2A is recruited to the Myog promoter at the onset of differentiation. This binding is essential to promote the demethylation of H3K9me2 and H3K9me3. We conclude that induction of the ΔN-JMJD2A isoform is crucial for muscle differentiation: by directing the removal of repressive chromatin marks at the Myog promoter, it promotes transcriptional activation of the Myog gene and thus contributes to initiation of muscle-specific gene expression.

Vyšlo v časopise: A New Isoform of the Histone Demethylase JMJD2A/KDM4A Is Required for Skeletal Muscle Differentiation. PLoS Genet 7(6): e32767. doi:10.1371/journal.pgen.1001390
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001390

Souhrn

Zdroje

1. AllisCD

BergerSL

CoteJ

DentS

JenuwienT

2007

New nomenclature for chromatin-modifying enzymes.

Cell

131

633

636

2. ShiY

LanF

MatsonC

MulliganP

WhetstineJR

2004

Histone demethylation mediated by the nuclear amine oxidase homolog LSD1.

Cell

119

941

953

3. CloosPA

ChristensenJ

AggerK

MaiolicaA

RappsilberJ

2006

The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3.

Nature

442

307

311

4. CoutureJF

CollazoE

Ortiz-TelloPA

BrunzelleJS

TrievelRC

2007

Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase.

Nat Struct Mol Biol

689

695

5. FodorBD

KubicekS

YonezawaM

O'SullivanRJ

SenguptaR

2006

Jmjd2b antagonizes H3K9 trimethylation at pericentric heterochromatin in mammalian cells.

Genes Dev

1557

1562

6. KloseRJ

YamaneK

BaeY

ZhangD

Erdjument-BromageH

2006

The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36.

Nature

442

312

316

7. WhetstineJR

NottkeA

LanF

HuarteM

SmolikovS

2006

Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases.

Cell

125

467

481

8. WissmannM

YinN

MullerJM

GreschikH

FodorBD

2007

Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression.

Nat Cell Biol

347

353

9. AggerK

CloosPA

ChristensenJ

PasiniD

RoseS

2007

UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development.

Nature

449

731

734

10. LanF

BaylissPE

RinnJL

WhetstineJR

WangJK

2007

A histone H3 lysine 27 demethylase regulates animal posterior development.

Nature

449

689

694

11. LohYH

ZhangW

ChenX

GeorgeJ

NgHH

2007

Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells.

Genes Dev

2545

2557

12. ZhangD

YoonHG

WongJ

2005

JMJD2A is a novel N-CoR-interacting protein and is involved in repression of the human transcription factor achaete scute-like homologue 2 (ASCL2/Hash2).

Mol Cell Biol

6404

6414

13. GraySG

IglesiasAH

LizcanoF

VillanuevaR

CameloS

2005

Functional characterization of JMJD2A, a histone deacetylase- and retinoblastoma-binding protein.

J Biol Chem

280

28507

28518

14. ShinS

JanknechtR

2007

Activation of androgen receptor by histone demethylases JMJD2A and JMJD2D.

Biochem Biophys Res Commun

359

742

746

15. GuasconiV

PuriPL

2009

Chromatin: the interface between extrinsic cues and the epigenetic regulation of muscle regeneration.

Trends Cell Biol

286

294

16. CaoY

KumarRM

PennBH

BerkesCA

KooperbergC

2006

Global and gene-specific analyses show distinct roles for Myod and Myog at a common set of promoters.

Embo J

502

511

17. SartorelliV

CarettiG

2005

Mechanisms underlying the transcriptional regulation of skeletal myogenesis.

Curr Opin Genet Dev

528

535

18. CarettiG

Di PadovaM

MicalesB

LyonsGE

SartorelliV

2004

The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation.

Genes Dev

2627

2638

19. SeenundunS

RampalliS

LiuQC

AzizA

PaliiC

2010

UTX mediates demethylation of H3K27me3 at muscle-specific genes during myogenesis.

EMBO J

20. RampalliS

LiL

MakE

GeK

BrandM

2007

p38 MAPK signaling regulates recruitment of Ash2L-containing methyltransferase complexes to specific genes during differentiation.

Nat Struct Mol Biol

1150

1156

21. ZhangCL

McKinseyTA

OlsonEN

2002

Association of class II histone deacetylases with heterochromatin protein 1: potential role for histone methylation in control of muscle differentiation.

Mol Cell Biol

7302

7312

22. GillespieMA

Le GrandF

ScimeA

KuangS

von MaltzahnJ

2009

p38-{gamma}-dependent gene silencing restricts entry into the myogenic differentiation program.

J Cell Biol

187

991

1005

23. MalAK

2006

Histone methyltransferase Suv39h1 represses MyoD-stimulated myogenic differentiation.

Embo J

3323

3334

24. BlaisA

TsikitisM

Acosta-AlvearD

SharanR

KlugerY

2005

An initial blueprint for myogenic differentiation.

Genes Dev

553

569

25. MoranJL

LiY

HillAA

MountsWM

MillerCP

2002

Gene expression changes during mouse skeletal myoblast differentiation revealed by transcriptional profiling.

Physiol Genomics

103

111

26. ShinS

JanknechtR

2007

Diversity within the JMJD2 histone demethylase family.

Biochem Biophys Res Commun

353

973

977

27. CalkhovenCF

MullerC

LeutzA

2000

Translational control of C/EBPalpha and C/EBPbeta isoform expression.

Genes Dev

1920

1932

28. LeeJ

ThompsonJR

BotuyanMV

MerG

2008

Distinct binding modes specify the recognition of methylated histones H3K4 and H4K20 by JMJD2A-tudor.

Nat Struct Mol Biol

109

111

29. BarskiA

CuddapahS

CuiK

RohTY

SchonesDE

2007

High-resolution profiling of histone methylations in the human genome.

Cell

129

823

837

30. ChoiJ

JangH

KimH

KimS

ChoE

2010

Histone demethylase LSD1 is required to induce skeletal muscle differentiation by regulating myogenic factors.

Biochem Biophys Res Commun

401

327

332

31. PetrieK

GuidezF

HowellL

HealyL

WaxmanS

2003

The histone deacetylase 9 gene encodes multiple protein isoforms.

J Biol Chem

278

16059

16072

32. ZhangCL

McKinseyTA

OlsonEN

2001

The transcriptional corepressor MITR is a signal-responsive inhibitor of myogenesis.

Proc Natl Acad Sci U S A

7354

7359

33. MejatA

RamondF

Bassel-DubyR

KhochbinS

OlsonEN

2005

Histone deacetylase 9 couples neuronal activity to muscle chromatin acetylation and gene expression.

Nat Neurosci

313

321

34. ZibettiC

AdamoA

BindaC

FornerisF

ToffoloE

2010

Alternative splicing of the histone demethylase LSD1/KDM1 contributes to the modulation of neurite morphogenesis in the mammalian nervous system.

J Neurosci

2521

2532

35. LoisS

BlancoN

Martinez-BalbasM

de la CruzX

2007

The functional modulation of epigenetic regulators by alternative splicing.

BMC Genomics

252

36. JeanE

Laoudj-ChenivesseD

NotarnicolaC

RougerK

SerratriceN

2009

Aldehyde dehydrogenase activity promotes survival of human muscle precursor cells.

J Cell Mol Med

37. VandrommeM

ChailleuxC

EscaffitF

TroucheD

2008

Binding of the Retinoblastoma Protein Is Not the Determinant for Stable Repression of Some E2F-Regulated Promoters in Muscle Cells.

Mol Cancer Res

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