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
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
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