The SAGA continues: expanding the cellular role of a transcriptional co-activator complex.
Throughout the last decade, great advances have been made in our understanding of how DNA-templated cellular processes occur in the native chromatin environment. Proteins that regulate transcription, replication, DNA repair, mitosis and other processes must be targeted to specific regions of the genome and granted access to DNA, which is normally tightly packaged in the higher-order chromatin structure of eukaryotic nuclei. Massive multiprotein complexes have been discovered, which facilitate access to DNA and recruitment of downstream effectors through three distinct mechanisms: chemical modification of histone amino-acid residues, ATP-dependent chromatin remodeling and histone exchange. The yeast Spt-Ada-Gcn5-Acetyl transferase (SAGA) transcriptional co-activator complex regulates numerous cellular processes through coordination of multiple histone post-translational modifications. SAGA is known to generate and interact with a number of histone modifications, including acetylation, methylation, ubiquitylation and phosphorylation. Although best characterized for its role in regulating transcriptional activation, SAGA is also required for optimal transcription elongation, mRNA export and perhaps nucleotide excision repair. Here, we discuss findings from recent years that have elucidated the function of this 1.8-MDa complex in multiple cellular processes, and how misregulation of the homologous complexes in humans may ultimately play a role in development of disease.
Baker
S P
SP
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Grant
P A
PA
D000107:Acetylation; D002843:Chromatin / Q000378:metabolism*; D004194:Disease; D010450:Endopeptidases / Q000378:metabolism; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic
D002843:Chromatin; D006657:Histones; C507785:SAGA complex, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D051548:Histone Acetyltransferases; D010450:Endopeptidases; D046988:Proteasome Endopeptidase Complex; C119011:26S proteasome non-ATPase regulatory subunit 13
Nature. 2005 Dec 22;438(7071):1181-5
16372014
Nucleic Acids Res. 2006;34(3):976-85
16473851
Mol Cell Biol. 2006 May;26(9):3339-52
16611979
Mol Cell Biol. 2006 Jun;26(11):4095-110
16705163
Cell. 2006 May 19;125(4):703-17
16713563
Nature. 2006 Jun 8;441(7094):770-3
16760982
Mol Biol Cell. 2006 Oct;17(10):4228-36
16855026
Nucleic Acids Res. 2006;34(21):6225-32
17090597
J Mol Biol. 2007 Jan 26;365(4):1047-62
17098252
Mol Cell. 2007 Jan 12;25(1):31-42
17218269
Mol Cell Biol. 2007 May;27(9):3405-16
17325035
Mutat Res. 2007 May 1;618(1-2):81-90
17306843
Oncogene. 2007 Aug 13;26(37):5341-57
17694077
Oncogene. 2007 Aug 13;26(37):5358-72
17694078
Cell Cycle. 2005 Jul;4(7):919-26
15970672
Genes Dev. 1999 Nov 15;13(22):2940-5
10580001
Mol Cell Biol. 2000 Jan;20(2):556-62
10611234
EMBO J. 1994 Oct 17;13(20):4807-15
7957049
Genetics. 1995 Feb;139(2):523-36
7713415
Nature. 2002 Jan 10;415(6868):141-7
11805826
Oncogene. 2002 Feb 21;21(9):1411-22
11857084
Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6364-8
7603997
Cell. 1996 Mar 22;84(6):843-51
8601308
Mol Cell Biol. 1996 Jun;16(6):3197-205
8649430
Annu Rev Biochem. 1996;65:769-99
8811195
Mol Cell Biol. 1997 Mar;17(3):1110-7
9032238
Genes Dev. 1997 Jul 1;11(13):1640-50
9224714
Hum Mol Genet. 1998 Feb;7(2):165-70
9425222
Nature. 1998 Feb 12;391(6668):715-8
9490418
Cell. 1998 Jul 10;94(1):45-53
9674426
Nature. 1998 Jul 30;394(6692):498-502
9697775
Cell. 1998 Aug 7;94(3):363-74
9708738
J Biol Chem. 1998 Oct 9;273(41):26559-65
9756893
Mol Cell Biol. 1999 Jan;19(1):86-98
9858534
Mol Cell Biol. 1999 Jan;19(1):855-63
9858608
Mol Cell. 1998 Dec;2(6):863-7
9885573
Mol Cell. 1999 Jun;3(6):687-95
10394357
Trends Biochem Sci. 2005 Jan;30(1):7-10
15653319
Mol Cell Biol. 2005 Feb;25(3):1162-72
15657441
Mol Cell Biol. 2005 Feb;25(3):1173-82
15657442
Nature. 2005 Jan 27;433(7024):434-8
15647753
EMBO J. 2005 Mar 9;24(5):997-1008
15719021
J Mol Endocrinol. 2005 Apr;34(2):281-97
15821097
Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8472-7
15932940
Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8478-82
15932941
Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8650-5
15939881
J Biol Chem. 2002 Mar 8;277(10):7989-95
11773077
Mol Cell Biol. 2005 Oct;25(20):9092-102
16199885
Mol Cell. 2005 Oct 28;20(2):199-211
16246723
Cell. 2005 Nov 4;123(3):361-3
16269325
Cell. 2005 Nov 4;123(3):423-36
16269334
J Biol Chem. 2005 Dec 23;280(51):41789-92
16263726
Mol Cell Biol. 2000 Jan;20(2):634-47
10611242
Nature. 2000 Jan 6;403(6765):41-5
10638745
Trends Biochem Sci. 2000 Feb;25(2):59-63
10664584
J Dermatol Sci. 2000 May;23(1):1-11
10699759
EMBO J. 2000 Feb 1;19(3):410-20
10722314
Mol Biol Cell. 2000 Jun;11(6):2103-15
10848632
Mol Cell. 2000 Jun;5(6):905-15
10911985
Mol Cell. 2000 Jun;5(6):917-26
10911986
Nat Genet. 2000 Oct;26(2):229-32
11017084
Mol Cell. 2001 May;7(5):981-91
11389845
EMBO J. 2001 Jun 15;20(12):3187-96
11406595
Science. 2001 Jun 22;292(5525):2333-7
11423663
Yeast. 2001 Jul;18(10):889-95
11447594
Genes Dev. 2001 Aug 1;15(15):1946-56
11485989
Science. 2001 Aug 10;293(5532):1142-6
11498592
Mol Cell Biol. 2001 Oct;21(20):6782-95
11564863
Mol Cell Biol. 2002 Jun;22(12):4033-42
12024017
Nature. 2002 Jul 4;418(6893):104-8
12077605
Mol Cell Biol. 2002 Aug;22(15):5367-79
12101232
Nature. 2002 Aug 1;418(6897):498
12152067
J Biol Chem. 2002 Aug 9;277(32):28368-71
12070136
Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11622-7
12186975
Nature. 2002 Sep 26;419(6905):407-11
12353038
EMBO J. 2002 Nov 1;21(21):5843-52
12411502
Cell. 2002 Nov 1;111(3):369-79
12419247
Mol Cell Biol. 2002 Dec;22(24):8774-86
12446794
Mol Cell. 2003 Jan;11(1):261-6
12535538
Mol Cell. 2003 Jan;11(1):267-74
12535539
Nat Rev Mol Cell Biol. 2003 Mar;4(3):192-201
12612638
J Biol Chem. 2003 May 30;278(22):20405-12
12660246
Mol Cell. 2003 Aug;12(2):461-73
14536085
Genes Dev. 2003 Nov 1;17(21):2648-63
14563679
J Biol Chem. 2004 Jan 16;279(3):1867-71
14660634
Cell. 2004 Jan 9;116(1):75-86
14718168
Genes Dev. 2004 Feb 1;18(3):333-43
14871930
Mol Cell. 2004 Feb 13;13(3):435-42
14967150
Mol Cell. 2004 Feb 27;13(4):573-85
14992726
Mol Cell. 2004 Apr 9;14(1):1-15
15068799
Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5904-9
15069196
Hum Mol Genet. 2004 Jun 15;13(12):1257-65
15115762
Mol Cell. 2004 Jul 23;15(2):199-208
15260971
Mol Cell Biol. 2004 Aug;24(16):7249-59
15282323
Bioessays. 2004 Oct;26(10):1076-87
15382140
Cell. 1989 Sep 22;58(6):1183-91
2673545
Cell. 1992 Jul 24;70(2):251-65
1638630
Trends Genet. 1992 Nov;8(11):387-91
1332230
Genetics. 1994 Jul;137(3):647-57
8088510