Transcriptional inhibition of genes with severe histone H3 hypoacetylation in the coding region

被引:100
作者
Kristjuhan, A
Walker, J
Suka, N
Grunstein, M
Roberts, D
Cairns, BR
Svejstrup, JQ [1 ]
机构
[1] Imperial Canc Res Fund, Clare Hall Labs, Canc Res UK London Res Inst, Mechanisms Transcript Lab, S Mimms EN6 3LD, Herts, England
[2] Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA
[4] Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA
[5] Univ Utah, Huntsman Canc Inst, Howard Hughes Med Inst, Salt Lake City, UT 84112 USA
关键词
D O I
10.1016/S1097-2765(02)00647-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Changes in histone acetylation at promoters correlate with transcriptional activation and repression, but whether acetylation of histones in the coding region of genes is important for transcription is less clear. Here, we show that cells lacking the histone acetyl-transferases Gcn5 and Elp3 have widespread and severe histone H3 hypoacetylation in chromatin. Surprisingly, severe hypoacetylation in the promoter does not invariably affect the ability of TBP to bind the TATA element, or transcription of the gene. By contrast, similar hypoacetylation of the coding region correlates with inhibition of transcription, and inhibition correlates better with the overall charge of the histone H3 tail than with hypoacetylation of specific lysine residues. These data provide insights into the effects of histone H3 hypoacetylation in vivo and underscore the importance of the overall charge of the histone tail for transcription.
引用
收藏
页码:925 / 933
页数:9
相关论文
共 52 条
[1]   Reduced levels of histone H3 acetylation on the inactive X chromosome in human females [J].
Boggs, BA ;
Connors, B ;
Sobel, RE ;
Chinault, AC ;
Allis, CD .
CHROMOSOMA, 1996, 105 (05) :303-309
[2]   ACETYLATED HISTONE H4 ON THE MALE X-CHROMOSOME IS ASSOCIATED WITH DOSAGE COMPENSATION IN DROSOPHILA [J].
BONE, JR ;
LAVENDER, J ;
RICHMAN, R ;
PALMER, MJ ;
TURNER, BM ;
KURODA, MI .
GENES & DEVELOPMENT, 1994, 8 (01) :96-117
[3]   X-chromosome inactivation and the search for chromosome-wide silencers [J].
Cohen, DE ;
Lee, JT .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2002, 12 (02) :219-224
[4]   Regulation of transcription by H1 phosphorylation in Tetrahymena is position independent and requires clustered sites [J].
Dou, YL ;
Gorovsky, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (09) :6142-6146
[5]   Histone acetylation: a switch between repressive and permissive chromatin - Second in review series on chromatin dynamics [J].
Eberharter, A ;
Becker, PB .
EMBO REPORTS, 2002, 3 (03) :224-229
[6]   2 DISTINCT YEAST TRANSCRIPTIONAL ACTIVATORS REQUIRE THE FUNCTION OF THE GCN5 PROTEIN TO PROMOTE NORMAL LEVELS OF TRANSCRIPTION [J].
GEORGAKOPOULOS, T ;
THIREOS, G .
EMBO JOURNAL, 1992, 11 (11) :4145-4152
[7]   Yeast Gcn5 functions in two multisubunit complexes to acetylate nucleosomal histones: Characterization of an Ada complex and the SAGA (Spt/Ada) complex [J].
Grant, PA ;
Duggan, L ;
Cote, J ;
Roberts, SM ;
Brownell, JE ;
Candau, R ;
Ohba, R ;
OwenHughes, T ;
Allis, CD ;
Winston, F ;
Berger, SL ;
Workman, JL .
GENES & DEVELOPMENT, 1997, 11 (13) :1640-1650
[8]   Histone acetyltransferase complexes stabilize SWI/SNF binding to promoter nucleosomes [J].
Hassan, AH ;
Neely, KE ;
Workman, JL .
CELL, 2001, 104 (06) :817-827
[9]   Dissecting the regulatory circuitry of a eukaryotic genome [J].
Holstege, FCP ;
Jennings, EG ;
Wyrick, JJ ;
Lee, TI ;
Hengartner, CJ ;
Green, MR ;
Golub, TR ;
Lander, ES ;
Young, RA .
CELL, 1998, 95 (05) :717-728
[10]   Histone H3 specific acetyltransferases are essential for cell cycle progression [J].
Howe, L ;
Auston, D ;
Grant, P ;
John, S ;
Cook, RG ;
Workman, JL ;
Pillus, L .
GENES & DEVELOPMENT, 2001, 15 (23) :3144-3154