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Requirement of Male-Specific Dosage Compensation in Females—Implications of Early X Chromosome Gene Expression


Dosage compensation equates between the sexes the gene dose of sex chromosomes that carry substantially different gene content. In Drosophila, the single male X chromosome is hypertranscribed by approximately two-fold to effect this correction. The key genes are male lethal and appear not to be required in females, or affect their viability. Here, we show these male lethals do in fact have a role in females, and they participate in the very process which will eventually shut down their function—female determination. We find the male dosage compensation complex is required for upregulating transcription of the sex determination master switch, Sex-lethal, an X-linked gene which is specifically activated in females in response to their two X chromosomes. The levels of some X-linked genes are also affected, and some of these genes are used in the process of counting the number of X chromosomes early in development. Our data suggest that before the female state is set, the ground state is male and female X chromosome expression is elevated. Females thus utilize the male dosage compensation process to amplify the signal which determines their fate.


Vyšlo v časopise: Requirement of Male-Specific Dosage Compensation in Females—Implications of Early X Chromosome Gene Expression. PLoS Genet 6(7): e32767. doi:10.1371/journal.pgen.1001041
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001041

Souhrn

Dosage compensation equates between the sexes the gene dose of sex chromosomes that carry substantially different gene content. In Drosophila, the single male X chromosome is hypertranscribed by approximately two-fold to effect this correction. The key genes are male lethal and appear not to be required in females, or affect their viability. Here, we show these male lethals do in fact have a role in females, and they participate in the very process which will eventually shut down their function—female determination. We find the male dosage compensation complex is required for upregulating transcription of the sex determination master switch, Sex-lethal, an X-linked gene which is specifically activated in females in response to their two X chromosomes. The levels of some X-linked genes are also affected, and some of these genes are used in the process of counting the number of X chromosomes early in development. Our data suggest that before the female state is set, the ground state is male and female X chromosome expression is elevated. Females thus utilize the male dosage compensation process to amplify the signal which determines their fate.


Zdroje

1. LucchesiJC

KellyWG

PanningB

2005 Chromatin remodeling in dosage compensation. Annual Review of Genetics 39 615 51

2. FukunagaA

TanakaA

OishiK

1975 Maleless, a recessive autosomal mutant of Drosophila melanogaster that specifically kills male zygotes. Genetics 81 135 141

3. BeloteJ

LucchesiJC

1980 Male-specific lethal mutations of Drosophila melanogaster. Genetics 96 165 186

4. UchidaS

UenoyamaT

OishiK

1981 Studies on the sex-specific lethal of Drosophila melanogaster III. A third chromosome male-specific lethal mutant. Jpn J Genet 56 523 527

5. HilfickerA

Hilfiker-KleinerD

PannutiA

LucchesiJC

1997 mof, a putative acetyl transferase gene related to the Tip60 and MOZ human genes and to the SAS genes of yeast, is required for dosage compensation in Drosophila. EMBO J 16 2054 2060

6. KelleyRL

2004 Path to equality strewn with roX. Dev Biol 269 18 25

7. GelbartME

KurodaMI

2009 Drosophila dosage compensation: a complex voyage to the X chromosome. Development 136 1399 1410

8. FrankeA

BakerBS

1999 The roX1 and roX2 RNAs Are Essential Components of the Compensasome, which Mediates Dosage Compensation in Drosophila. Mol Cell 4 117 122

9. MellerVH

2003 Initiation of dosage compensation in Drosophila embryos depends on expression of the roX RNAs. Mech Dev 120 759 67

10. JinY

WangY

WalkerDL

DongH

ConleyC

1999 JIL-1: A Novel Chromosomal Tandem Kinase Implicated in Transcriptional Regulation in Drosophila. Mol Cell 4 129 135

11. SkripskyT

LucchesiJC

1980 Females with sex-combs. Genetics 94 s98 s99

12. UenoyamaT

FukunagaA

OishiK

1982 Studies on the sex-specific lethals of Drosophila melanogaster V. sex transformation caused by interactions between a female-specific lethal, Sxlf#1, and the male-specific lethals mle(3)132, ms1-227, and mle. Genetics 102 233 243

13. BashawGJ

BakerBS

1995 The msl-2 dosage compensation gene of Drosophila encodes a putative DNA-binding protein whose expression is sex specifically regulated by Sex-lethal. Development 121 3245 58

14. BashawGJ

BakerBS

1997 The regulation of the Drosophila msl-2 gene reveals a function for Sex-lethal in translational control. Cell 89 789 798

15. KelleyRL

SolovyevaI

LymanLM

RichmanR

SolovyevV

1995 Expression of msl-2 causes assembly of dosage compensation regulators on the X chromosomes and female lethality in Drosophila. Cell 81 867 877

16. KelleyRL

WangJ

BellL

KurodaMI

1997 Sex lethal controls dosage compensation in Drosophila by a non-splicing mechanism. Nature 387 195 199

17. ZhouS

YangY

ScottMJ

PannutiA

FehrKC

1999 Male-specific lethal 2, a dosage compensation gene of Drosophila, undergoes sex-specific regulation and encodes a protein with a RING finger and a metallothionein-like cysteine cluster. EMBO J 14 2884 2895

18. KeyesLN

ClineTW

SchedlP

1992 The Primary Sex Determination Signal of Drosophila Acts at the Level of Transcription. Cell 68 933 943

19. SchuttC

NothigerR

2000 Structure, function and evolution of sex-determining systems in Dipteran insects. Development 127 667 677

20. BellL

HorabinJ

SchedlP

ClineT

1991 Positive autoregulation of Sex-lethal by alternative splicing maintains the female determined state in Drosophila. Cell 65 229 239

21. KindJ

AkhtarA

2007 Cotranscriptional recruitment of the dosage compensation complex to X-linked target genes. Genes Dev 21 2030 2040

22. BaiX

AlekseyenkoAA

KurodaMI

2004 Sequence-specific targeting of MSL complex regulates transcription of the roX RNA genes. EMBO J 23 2853 61

23. AvilaFW

EricksonJW

2007 Drosophila JAK/STAT pathway reveals distinct initiation and reinforcement steps in early transcription of Sxl. Curr Biol 17 643 648

24. LiF

SchiemannAH

ScottMJ

2008 Incorporation of the noncoding roX RNAs alters the chromatin-binding specificity of the Drosophila MSL1/MSL2 complex. Mol Cell Biol 28 1252 64

25. EricksonJW

ClineTW

1993 A bZIP protein, sisterless-a, collaborates with bHLH transcription factors early in Drosophila development to determine sex. Genes Dev 7 1688 1702

26. ten BoschJR

BenavidesJA

ClineTW

2006 The TAGteam DNA motif controls the timing of Drosophila pre-blastoderm transcription. Development 133 1967 1977

27. De RenzisS

ElementoO

TavazoieS

WieschausEF

2007 Unmasking activation of the zygotic genome using chromosomal deletions in the Drosophila embryo. PLoS Biol 5 e117 doi:10.1371/journal.pbio.0050117. Erratum in: PLoS Biol 8:e213.doi:10.1371/journal.pbio.0050213

28. RastelliL

RichmanR

KurodaMI

1995 The dosage compensation regulators MLE, MSL-1 and MSL-2 are interdependent since early embryogenesis in Drosophila. Mech Dev 53 223 33

29. FrankeA

DernburgA

BashawGJ

BakerBS

1996 Evidence that MSL-mediated dosage compensation in Drosophila begins at blastoderm. Development 122 2751 60

30. McDowellKA

HilfikerA

LucchesiJC

1996 Dosage compensation in Drosophila: the X chromosome binding of MSL-1 and MSL-2 in female embryos is prevented by the early expression of the Sxl gene. Mech Dev 57 113 9

31. AlekseyenkoAA

LarschanE

LaiWR

ParkPJ

KurodaMI

2006 High-resolution ChIP–chip analysis reveals that the Drosophila MSL complex selectively identifies active genes on the male X chromosome. Genes Dev 20 848 857

32. ClineT

1984 Autoregulatory functioning of a Drosophila gene product that establishes and maintains the sexually determined state. Genetics 107 231 277

33. GergenJP

1987 Dosage Compensation in Drosophila: Evidence That daughterless and Sex-lethal Control X Chromosome Activity at the Blastoderm Stage of Embryogenesis. Genetics 117 477 485

34. SmithER

AllisCD

LucchesiJC

2001 Linking global histone acetylation to the transcription enhancement of X-chromosomal genes in Drosophila males. J Biol Chem 276 31483 31486

35. AlekseyenkoAA

PengS

LarschanE

GorchakovAA

LeeO

2008 A Sequence Motif within Chromatin Entry Sites Directs MSL Establishment on the Drosophila X Chromosome. Cell 134 599 609

36. StraubT

GrimaudC

GilfillanGD

MitterwegerA

BeckerPB

2008 The Chromosomal High-Affinity Binding Sites for the Drosophila Dosage Compensation Complex. PLoS Genetics 4 e1000302 doi:10.1371/journal.pgen.1000302

37. Younger-ShepherdS

VaessinH

BierE

JanLY

JanYN

1992 deadpan, an essential pan-neural gene encoding an HLH protein, acts as a denominator in Drosophila sex determination. Cell 70 911 922

38. BarbashDA

ClineTW

1995 Genetic and molecular analysis of the autosomal component of the primary sex determination signal of Drosophila melanogaster. Genetics 141 1451 71

39. AronsonBD

FisherAL

BlechmanK

CaudyM

GergenJP

1997 Groucho-dependent and -independent repression activities of Runt domain proteins. Mol Cell Biol 17 5581 7

40. GiotL

BaderJS

BrouwerC

ChaudhuriA

KuangB

2003 A protein interaction map of Drosophila melanogaster. Science 302 1727 36

41. KramerSG

JinksTM

SchedlP

GergenJP

1999 Direct activation of Sex-lethal transcription by the Drosophila runt protein. Development 126 191 200

42. GuptaV

ParisiM

SturgillD

NuttallR

DoctoleroM

2006 Global analysis of X-chromosome dosage compensation. J Biol 5 3

43. NguyenDK

DistecheCM

2006 Dosage compensation of the active X chromosome in mammals. Nat.Genet 38 47 53

44. LinH

GuptaV

VermilyeaMD

FalcianiF

LeeJT

2007 Dosage compensation in the mouse balances up-regulation and silencing of X-linked genes. PLoS Biol 5 e326 doi:10.1371/journal.pbio.0050326

45. WalthallSL

MosesM

HorabinJI

2007 A large complex containing both Patched and Smoothened initiates Hedgehog signaling in Drosophila. J Cell Science 120 826 837

46. MendjanS

TaipaleM

KindJ

HolzH

GebhardtP

2006 Nuclear pore components are involved in the transcriptional regulation of dosage compensation in Drosophila. Mol Cell 21 811 23

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