Abf1 (37)

RNA polymerase II (13)

3

RNA polymerase III (13)

3

Azf1 (2)

Cdc28p complexes (10)

2

Bck2 (2)

2

Cbf1 (16)

Cytochrome bc1 complex (10)

2

Cln3 (2)

2

Dun1 (3)

Ribonucleoside diphosphate reductase (4)

3

Far1 (2)

2

Fau1 (3)

Glycine decarboxylase (4)

3

Gcn4 (40)

Anthranilate synthase (2)

22

Gcr1 (18)

Cytoplasmic translation elongation (9)

2

eEF1 (6)

2

Hap2 (14)

2-oxoglutarate dehydrogenase (3)

2

Hap3 (15)

2

Hap4 (14)

3

Hir1 (4)

Nucleosomal protein complex (8)

4

Hir2 (2)

2

Hir3 (3)

3

Hta1 (2)2

Hta2 (2)

2

Ime4 (1)

Ume6 Ime1 complex (2)

1

Ino2 (19)

Fatty acid synthetase cytoplasmic (2)

2

Ino4 (19)

2

Mbp1 (6)

2

Mcm1 (14)3

Pre replication complex (14)

2

Mig1 (26)

GAL80_complex (3)

2

Msn2 (56)

Alpha_alpha-trehalose-phosphate_synthase (4)

3

Msn4 (58)

3

Ndt80 (11)5

Rad26 (1)

1

Rad9 (2)

2

Rap1 (32) 2

Reb1 (19)

2

Rfx1 (5)

3

Rpn4 (11)

19-22S regulator (18)

6

20S proteasome (15)

2

Rtg1 (12)

Isocitrate dehydrogenase (2)

2

Rtg3 (6)

2

Sit4 (2) 2

Spt10 (3)

2

Spt16 (2)

2

Spt21 (3)

2

Stb1 (1)

MBF_complex (2)

1

SBF complex (2)

1

Swi4 (8)

2

Glucan synthases (5)

2

Swi6 (10)3

Tup1 (7)

3

Xbp1 (5)

3

Yhp1 (1)

1

Yku70 (2)

2

a b

c

Respiration chain complexes(37)

Figure S1 : Network graph built using statistically significant (E-value<0.1) overlaps between annotated complexes from the CYGD database and annotated regulons (see main manuscript for details).Complexes are denoted by their name in the CYGD database and regulons by the common name ofthe transcription factor which bind it.Each node represents a complex (red ellipses) or a regulon (blue rectangles). The number of genes ineach group (complex or regulon) is given in parentheses. The number of genes common to a givencomplex-regulon pair is indicated along the lines (arc) joining the pair. a,b,c clusters are detailed in themain manuscript.

Abf1 (282)

RNA polymerase III (13)

5

Bas1 (44)

Glycine decarboxylase (4)

3

Fhl1 (194)

cytoplasmic ribosomal large subunit (81)

67

cytoplasmic ribosomal small subunit (57)

53

Gal4 (40)

GAL80 complex (3)

2

Gat1 (1)

Dynactin complex (3)

1

Gcn4 (80)

Arginine-specific carbamoylphosphate synthase (2)

2

Hap2 (19)

Cytochrome bc1 complex (9)

2Cytochrome c oxidase (8)

2

Hap3 (23)

2

Hap4 (69)

78

F0 F1 ATP synthase (15)

10

Hir1 (30)

Nucleosomal protein complex (8)

6

Hir2 (21)

6

Ino2 (11)

Fatty acid synthetase cytoplasmic (2)

2

Ino4 (19)

2

Mbp1 (112)Cdc28p complexes (10)3

Mcm1 (89)

Alpha-agglutinin anchor (2)

2Pre-replication complex (14)3

Met4 (29)2

Pdr1 (69)

8

Rap1 (209)

46

30

Rfx1 (32)

Ribonucleoside diphosphate reductase (4)

3

Yap5 (107)

10

8

ab

2

Replication-complexes (49)

7

Replication-factor-A-complex (3)

Swi4 (136)

5

c

Figure S2 : Network graph built using statistically significant (E-value<0.1) overlaps between annotated complexes from the CYGD database and high-throughput regulons (see main manuscript for details).Notations are identical to figure S1. a,b,c clusters are detailed in the main manuscript.

CDC28

CLN1

CLN2

HMS407 (2/4)

TAP83 (3/10)

Cln3 (2/2)

Far1 (2/2)

Sit4 (2/2)Swi4 (2/8)

Spt16 (2/2)

Bck2 (2/2)

Swi6 (2/10)

b

SWI4RAD53

CLB2

CLB3

CLB5

HMS365 (2/18)

HMS468 (5/10)

HMS422 (2/7) HMS188 (2/2)Xbp1 (2/5)

Ndt80(2/11)

Mcm1 (3/14)

TPS1

ARA1

GRX1

TPS2

TRR1

TSA2

ADE6

YGR086C

ADE3

YAK1

SOD1

APE2UBA1

HSP104

AHP1

PGM2

ADE17

TPS3ADH2

DCS2

OYE3

GPH1

TAP31 (3/16)

HMS111 (3/10)

HMS210 (6/55)

HMS25 (3/26)

HMS26 (4/14)

HMS50 (5/45)

HMS84 (11/47)

Bas1 (3/17)

Msn2 (13/56)

Yap1 (8/32)Msn4 (13/58)

Pho2 (3/21)

d

Figure S3 : Detailed view of the genes linking clusters of protein complexes and high-throughputregulons. Each ellipse represents a high-throughput complex, which is denoted as detailed in the main manuscript. Regulons are surrounded by rectangles, and their intersections with complexes are displayed by rounded boxes.a) Permeases clusterb) Cyclin-protein kinase clusterc) Glycolysis, fermentation, and RNA polymerases clusterd) Stress response cluster

PGK1

TAP18 (2/3)

Sto1 (1/1)

Abf1 (8/37)

ENO2

Gcr1 (6/18)

Rap1 (7/32)

TPI1

ADH1

TAP139(6/43)

PDC1

HIS4

RPB2

SPT15

TDH3

FBA1

SIN3

SRP1

RP021

RPC40

RPO26

Gcr2 (4/11)

Tye7 (3/6)

Reb1 (3/19)

TAP186(2/5)

TAP145(3/19)

TAP159(5/50)

TAP62(5/13)TAP229(3/11)

TAP86(5/19)

TAP88(2/9)

c

HXT7

Swi1 (4/5)

HMS286 (2/38)HXT6

PHO84

PRB1

Snf2 (4/6)

HMS184 (2/18)

HMS286 (3/38)

HMS303 (2/3)

HMS98 (2/6)

HMS106 (2/8)

HMS29 (2/18)

Snf3 (1/1)

a

TAP105(20)Abf1(282)6

TAP111(73)

11

TAP115(29)

Dot6(9)

2

TAP133(2)

Hap4(69) 2

TAP144(4)

Hap2(19)

2

Hap3(23) 2 4

TAP146(35)

7

TAP15(3)

Hsf1(55)

2

TAP154(29)

7

TAP155(26)

Thi2(7)

2

TAP156(84)

15

TAP161(82) 3

TAP212(6)Rfx1(32)

2

TAP99(34)

7

HMS100(44)

Hir2(21)

3

HMS117(8)

Mac1(37)2

HMS150(14)

Hir1(30)3

3

HMS172(5)

22

HMS175(10)

2

HMS19(10)

Mbp1(112)

4

HMS200(3)

Pho4(62)

2

HMS250(4)Dig1(38)

2 2

2

Ste12(57)

2

HMS251(14)

3

3

HMS273(50)4

3

HMS28(2)

Rgt1(2)

1

HMS301(12)

3

HMS326(33)7

HMS349(8)

2

2

HMS360(4)

3

HMS397(10)

4

HMS424(5)

2

2

HMS461(5)

Rox1(32)

2

HMS468(10)

Fkh2(108)

3

HMS483(17)

3

HMS55(27)

3

HMS84(47)

Ino4(19)

3

b

a

c

Figure S4: Network graph built using statistically significant (E-value<0.1) overlaps betweencomplexes and the high throughput regulons identified by the genome-wide location analysis(Lee, et al., 2002). Notations are identical to Figure S1. a, b, c are detailed in figure S4.

ATP3

ATP5ATP7

COX4

COX5A

COX6

COX9

TAP133 (2/2)

TAP144 (4/4)

Hap2 (2/19)

Hap3 (3/23)

Hap4 (9/69) QCR2

COR1

HMS483 (3/17)

a

HHF1HHT1

HTA1

HTB1

NOC3

SUI2

Hir1 (6/21)

Hir2 (4/21)

HMS100 (3/44)

HMS150 (3/14)

HMS172 (2/5)

HMS251 (3/14)

HMS424(2/5)

HMS175(2/10)

HMS250 (2/4)

HMS273(4/50)

HMS349 (2/8)HMS55 (2/27)

TEC1

STE12 Ste12 (2/57)

Dig1 (2/38)

b

GCN1

TAP111 (11/73)

TAP105 (6/20)

NOP58

LTV1

ARP9

RRP12

YOR145C

YOR056C

SWI3

PTA1

REF2RNA14 SEC21

TIF1

YGR128C

YLR222CSOF1

YMR093W

TAP146 (7/35)

DHH1

FBA1

RET1

RPB10

RPC25

RPO26RPO31

TAP154 (7/29)

BRX1NOC2RRP7PNO1

TAP156 (15/84)

CCT8RPN10

RPN8

RPT5

YKT6URA7

TAP99 (7/34)

YLL034C

ECM33

IDH1MKT1

PMA2

HMS326 (7/33)

EBP2MSS116

HMS397 (4/10)

Abf1 (64/282)

c

Figure S5 : Detailed view of the genes linking clusters of protein complexes and high-throughputregulons. Each ellipse represents a high-throughput complex, which is denoted as detailed in the main manuscript. Regulons are surrounded by rectangles, and their intersections with complexes are displayed by rounded boxes.a) The 9 common genes are involved in respiration. COX4,COX5A,COX6 and COX9 code for components of cytochrome-c oxydase complex IV ; ATP3,ATP5,ATP7 for the F1F0-ATPase complex , and QCR2 and COR1 for ubiquinol--cytochrome-c reductase complex III. b) The Cluster involving Hir1 and Hir2 transcription factors shows 4/8 genes ,which code for histones, and 3 other genes that are involved in transcription and replication. c) The Big Abf1 regulons is significantly linked with 8 protein complexes. Numerous genes involved in this regulon are of unknown functions or show different functional annotations but a significant part of them are involved in rRNA or tRNA synthesis and processing (13/41).

TAP106 (14)

TAP148 (27)

TAP151 (17)

TAP157 (26)

HMS223 (13)

TAP111 (36)

TAP132 (33)

TAP146 (20)

TAP156 (44)

HMS373 (28)

HMS65 (15)

TAP126 (10)

HMS126 (7)

HMS161 (14)

HMS220 (14)

TAP163 (54)

HMS100 (20)

HMS136 (16)

HMS197 (9)

HMS218 (7)

HMS225 (10)

HMS273 (22)

HMS310 (12)

HMS372 (14)

HMS89 (15)TAP142 (9)

TAP77 (5)

HMS169 (8)

HMS396 (8)

HMS397 (7)

TAP4 (5)

HMS204 (4)

HMS104 (6)

HMS239 (10)

HMS150 (8)

HMS349 (3)

HMS162 (5)

HMS304 (3)

HMS25 (10)

HMS301 (7)

HMS358 (3)

HMS423 (4)

11

8

12

8

10

11

30

8

11

6

6 3 5

6

10

23

79

5

4

5

11

5

6

18

10

5

186

9

25

6

12

139

10

10

10

13

6

12

13

10

10

13

7

5

11

15

5

13

2 3

5

3 7

7

3

36

7

48

4

10

5

3

13

2

34 3

8

44

5

35

4

5

3

5

12

6

7

9

5

5

7

3

3

45 7

2

3

4

5

4

Figure S6: Network linking putative co-regulated genes in different high-throughput multiprotein complexes.Each node represents a group of putative co-regulated genes predicted for a given protein complex,using the combined approach of pattern discovery and discriminant analysis (see main manuscript).The complexes are denoted as in the main manuscript. The number of co-regulated genes in each complexis given in parentheses. The number of co-regulated genes that are in common between two complexes isdisplayed along the line (arc) joining the complexes.The network has two large clusters and a few small pair wise connections. The smaller of the large clusters (framed) corresponds to the complexes pertaining to the proteasome,as detailed in Fig. 7 of the main manuscript.