Essential Functions of the Histone Demethylase Lid

English version České info

Drosophila Little imaginal discs (Lid) is a recently described member of the JmjC domain class of histone demethylases that specifically targets trimethylated histone H3 lysine 4 (H3K4me3). To understand its biological function, we have utilized a series of Lid deletions and point mutations to assess the role that each domain plays in histone demethylation, in animal viability, and in cell growth mediated by the transcription factor dMyc. Strikingly, we find that lid mutants are rescued to adulthood by either wildtype or enzymatically inactive Lid expressed under the control of its endogenous promoter, demonstrating that Lid's demethylase activity is not essential for development. In contrast, ubiquitous expression of UAS-Lid transgenes lacking its JmjN, C-terminal PHD domain, and C₅HC₂ zinc finger were unable to rescue lid homozygous mutants, indicating that these domains carry out Lid's essential developmental functions. Although Lid-dependent demethylase activity is not essential, dynamic removal of H3K4me3 may still be an important component of development, as we have observed a genetic interaction between lid and another H3K4me3 demethylase, dKDM2. We also show that Lid's essential C-terminal PHD finger binds specifically to di- and trimethylated H3K4 and that this activity is required for Lid to function in dMyc-induced cell growth. Taken together, our findings highlight the importance of Lid function in the regulated removal and recognition of H3K4me3 during development.

Vyšlo v časopise: Essential Functions of the Histone Demethylase Lid. PLoS Genet 6(11): e32767. doi:10.1371/journal.pgen.1001221
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001221

Souhrn

Zdroje

1. BernsteinBE

HumphreyEL

ErlichRL

SchneiderR

BoumanP

2002 Methylation of histone H3 Lys 4 in coding regions of active genes. P Natl Acad Sci USA 99 8695 8700

2. BernsteinBE

KamalM

Lindblad-TohK

BekiranovS

BaileyDK

2005 Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 120 169 181

3. Santos-RosaH

SchneiderR

BannisterAJ

SherriffJ

BernsteinBE

2002 Active genes are tri-methylated at K4 of histone H3. Nature 419 407 411

4. SchneiderR

BannisterAJ

MyersFA

ThorneAW

Crane-RobinsonC

2004 Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nat Cell Biol 6 73 77

5. EissenbergJC

LeeMG

SchneiderJ

IlvarsonnA

ShiekhattarR

2007 The trithorax-group gene in Drosophila little imaginal discs encodes a trimethylated histone H3 Lys4 demethylase. Nat Struct Mol Biol 14 344 346

6. LeeN

Erdjument-BromageH

TempstP

JonesRS

ZhangY

2009 The H3K4 Demethylase Lid Associates with and Inhibits the Histone Deacetylase Rpd3. Mol Cell Biol 29 1401 1410

7. SecombeJ

LiL

CarlosLS

EisenmanRN

2007 The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase required for dMyc-induced cell growth. Gene Dev 21 537 551

8. ChristensenJ

AggerK

CloosPA

PasiniD

RoseS

2007 RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone H3. Cell 128 1063 1076

9. IwaseS

LanF

BaylissP

de la Torre-UbietaL

HuarteM

2007 The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell 128 1077 1088

10. KloseRJ

YanQ

TothovaZ

YamaneK

Erdjument-BromageH

2007 The Retinoblastoma binding protein RBP2 is a H3K4 demethylase. Cell 128 889 900

11. HayamiS

YoshimatsuM

VeerakumarasivamA

UnokiM

IwaiY

2010 Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway. Mol Cancer 9 59

12. XiangY

ZhuZ

HanG

YeX

XuB

2007 JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer. Proc Natl Acad Sci U S A 104 19226 19231

13. YamaneK

TateishiK

KloseRJ

FangJ

FabrizioLA

2007 PLU-1 is a H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation. Mol Cell 25 801 812

14. TahilianiM

MeiPC

FangR

LeonorT

RutenbergM

2007 The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation. Nature 447 601 605

15. GildeaJJ

LopezR

ShearnA

2000 A screen for new trithorax group genes identified little imaginal discs, the Drosophila melanogaster homologue of human retinoblastoma binding protein 2. Genetics 156 645 663

16. KortschakRD

TuckerPW

SaintR

2000 ARID proteins come in from the desert. Trends Biochem Sci 25 294 299

17. TuSJ

TengYC

YuanCH

WuYT

ChanMY

2008 The ARID domain of the H3K4 demethylase RBP2 binds to a DNA CCGCCC motif. Nat Struct Mol Biol 15 419 421

18. ScibettaAG

SantangeloS

ColemanJ

HallD

ChaplinT

2007 Functional analysis of the transcription repressor PLU-1/JARID1B. Mol Cell Biol 27 7220 7235

19. AaslandR

GibsonTJ

StewartAF

1995 The Phd Finger - Implications for Chromatin-Mediated Transcriptional Regulation. Trends Biochem Sci 20 56 59

20. TavernaSD

LiH

RuthenburgAJ

AllisCD

PatelDJ

2007 How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nat Struct Mol Biol 14 1025 1040

21. ChenZZ

ZangJY

WhetstineJ

HongX

DavrazouF

2006 Structural insights into histone demethylation by JMJD2 family members. Cell 125 691 702

22. LeeN

ZhangJY

KloseRJ

Erdjument-BromageH

TempstP

2007 The trithorax-group protein Lid is a histone H3 trimethyl-Lys4 demethylase. Nat Struct Mol Biol 14 341 343

23. Lloret-LlinaresM

CarreC

VaqueroA

de OlanoN

AzorinF

2008 Characterization of Drosophila melanogaster JmjC+N histone demethylases. Nucleic Acids Res 36 2852 2863

24. GreerEL

MauresTJ

HauswirthAG

GreenEM

LeemanDS

2010 Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans. Nature 466 383 387

25. KaviHH

BirchlerJA

2009 Drosophila KDM2 is a H3K4me3 demethylase regulating nucleolar organization. BMC Res Notes 2 217

26. LagarouA

Mohd-SaripA

MoshkinYM

ChalkleyGE

BezstarostiK

2008 dKDM2 couples histone H2A ubiquitylation to histone H3 demethylation during Polycomb group silencing. Genes Dev 22 2799 2810

27. PenaPV

DavrazouF

ShiXB

WalterKL

VerkhushaVV

2006 Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2. Nature 442 100 103

28. ShiXB

HongT

WalterKL

EwaltM

MichishitaE

2006 ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Nature 442 96 99

29. WangGG

SongJ

WangZ

DormannHL

CasadioF

2009 Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger. Nature 459 847 851

30. PengJC

ValouevA

SwigutT

ZhangJ

ZhaoY

2009 Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells. Cell 139 1290 1302

31. Lopez-BigasN

KisielTA

DeWaalDC

HolmesKB

VolkertTL

2008 Genome-wide analysis of the H3K4 histone demethylase RBP2 reveals a transcriptional program controlling differentiation. Mol Cell 31 520 530

32. GuccioneE

MartinatoF

FinocchiaroG

LuziL

TizzoniL

2006 Myc-binding-site recognition in the human genome is determined by chromatin context. Nat Cell Biol 8 764 U225

33. Di StefanoL

JiJY

MoonNS

HerrA

DysonN

2007 Mutation of Drosophila Lsd1 disrupts H3-K4 methylation, resulting in tissue-specific defects during development. Curr Biol 17 808 812

34. RudolphT

YonezawaM

LeinS

HeidrichK

KubicekS

2007 Heterochromatin formation in Drosophila is initiated through active removal of H3K4 methylation by the LSD1 homolog SU(VAR)3-3. Mol Cell 26 103 115

35. MoshkinYM

KanTW

GoodfellowH

BezstarostiK

MaedaRK

2009 Histone chaperones ASF1 and NAP1 differentially modulate removal of active histone marks by LID-RPD3 complexes during NOTCH silencing. Mol Cell 35 782 793

36. LiefkeR

OswaldF

AlvaradoC

Ferres-MarcoD

MittlerG

2010 Histone demethylase KDM5A is an integral part of the core Notch-RBP-J repressor complex. Genes Dev 24 590 601

37. TanakaY

OkamotoK

TeyeK

UmataT

YamagiwaN

2010 JmjC enzyme KDM2A is a regulator of rRNA transcription in response to starvation. Embo J 29 1510 1522

38. JungJ

MysliwiecMR

LeeY

2005 Roles of JUMONJI in mouse embryonic development. Dev Dynam 232 21 32

39. LiG

MargueronR

KuM

ChambonP

BernsteinBE

2010 Jarid2 and PRC2, partners in regulating gene expression. Genes Dev 24 368 380

40. PasiniD

CloosPA

WalfridssonJ

OlssonL

BukowskiJP

2010 JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells. Nature 464 306 310

41. LooLWM

SecombeJ

LittleJT

CarlosLS

YostC

2005 The transcriptional repressor dMnt is a regulator of growth in Drosophila melanogaster. Mol Cell Biol 25 7078 7091

42. JohnstonLA

ProberDA

EdgarBA

EisenmanRN

GallantP

1999 Drosophila myc regulates cellular growth during development. Cell 98 779 790

43. RadyukSN

MichalakK

KlichkoVI

BenesJ

RebrinI

2009 Peroxiredoxin 5 confers protection against oxidative stress and apoptosis and also promotes longevity in Drosophila. Biochem J 419 437 445

44. ZaffranS

ChartierA

GallantP

AstierM

ArquierN

1998 A Drosophila RNA helicase gene, pitchoune, is required for cell growth and proliferation and is a potential target of d-Myc. Development 125 3571 3584