The HOX homeodomain proteins block CBP histone acetyltransferase activity

被引:99
作者
Shen, WF
Krishnan, K
Lawrence, HJ
Largman, C
机构
[1] VA Med Ctr, Dept Med, San Francisco, CA 94121 USA
[2] VA Med Ctr, Dept Dermatol, San Francisco, CA 94121 USA
[3] Univ Calif San Francisco, San Francisco, CA 94143 USA
关键词
D O I
10.1128/MCB.21.21.7509-7522.2001
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
Despite the identification of PBC proteins as cofactors that provide DNA affinity and binding specificity for the HOX homeodomain proteins, HOX proteins do not demonstrate robust activity in transient-transcription assays and few authentic downstream targets have been identified for these putative transcription factors. During a search for additional cofactors, we established that each of the 14 HOX proteins tested, from 11 separate paralog groups, binds to CBP or p300. All six isolated homeodomain fragments tested bind to CBP, suggesting that the homeodomain is a common site of interaction. Surprisingly, CBP-p300 does not form DNA binding complexes with the HOX proteins but instead prevents their binding to DNA. The HOX proteins are not substrates for CBP histone acetyltransferase (HAT) but instead inhibit the activity of CBP in both in vitro and in vivo systems. These mutually inhibitory interactions are reflected by the inability of CBP to potentiate the low levels of gene activation induced by HOX proteins in a range of reporter assays. We propose two models for HOX protein function: (i) HOX proteins may function without CBP HAT to regulate transcription as cooperative DNA binding molecules with PBX, MEIS, or other cofactors, and (ii) the HOX proteins may inhibit CBP HAT activity and thus function as repressors of gene transcription.
引用
收藏
页码:7509 / 7522
页数:14
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