THE KRUPPEL-ASSOCIATED BOX-A (KRAB-A) DOMAIN OF ZINC-FINGER PROTEINS MEDIATES TRANSCRIPTIONAL REPRESSION

被引:333
作者
WITZGALL, R
OLEARY, E
LEAF, A
ONALDI, D
BONVENTRE, JV
机构
[1] MASSACHUSETTS GEN HOSP E,MED SERV,BOSTON,MA 02129
[2] HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115
关键词
TRANSCRIPTION FACTORS; KID-1; ZNF2; KIDNEY;
D O I
10.1073/pnas.91.10.4514
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have previously reported the cloning, sequencing, and partial characterization of Kid-1, a zinc finger-encoding cDNA from the rat kidney. The Kid-1 protein and approximately one-third of all other zinc finger proteins contain a highly conserved region of approximate to 75 amino acids at their NH2 terminus named Kruppel-associated box (KRAB), which is subdivided into A and B domains. The evolutionary conservation, wide distribution, and genomic organization of the KRAB domains suggest an important role of this region in the transcriptional regulatory function of zinc finger proteins. The functional significance of the KRAB domain was evaluated by studying transcriptional activities of yeast GAL4-rat Kid-1 fusion proteins containing various regions of the non-zinc-finger domain of Kid-1, Transcriptional repressor activity of GAL4-Kid-1 fusion proteins maps to the KRAB-A domain. The KRAB-A domain of another zinc finger protein, ZNF2, also has repressor activity. Site-directed mutagenesis of conserved amino acids in this moth results in decreased repressor activity. Thus, we have established a functional significance for the KRAB-A domain, a consensus sequence common in zinc finger proteins.
引用
收藏
页码:4514 / 4518
页数:5
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