Roles of cofactors and chromatin accessibility in Hox protein target specificity

Epigenetics & Chromatin

Robert White¹  Siew Woh Choo³  Steven Russell²  Aikaterini Chatzipli⁴  Sherif El-Sharnouby¹  Ching Yew Beh³ 

[1] Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK;Cambridge Systems Biology Centre, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK;Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, 50603, Malaysia;Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK

关键词: Transcription factor;    Chromatin accessibility;    Hox proteins;   

Others  :  1235285
DOI  :  10.1186/s13072-015-0049-x

 received in 2015-08-11, accepted in 2015-12-08,  发布年份 2016

【 摘 要 】

Background

The regulation of specific target genes by transcription factors is central to our understanding of gene network control in developmental and physiological processes yet how target specificity is achieved is still poorly understood. This is well illustrated by the Hox family of transcription factors as their limited in vitro DNA-binding specificity contrasts with their clear in vivo functional specificity.

Results

We generated genome-wide binding profiles for three Hox proteins, Ubx, Abd-A and Abd-B, following transient expression in Drosophila Kc167 cells, revealing clear target specificity and a striking influence of chromatin accessibility. In the absence of the TALE class homeodomain cofactors Exd and Hth, Ubx and Abd-A bind at a very similar set of target sites in accessible chromatin, whereas Abd-B binds at an additional specific set of targets. Provision of Hox cofactors Exd and Hth considerably modifies the Ubx genome-wide binding profile enabling Ubx to bind at an additional novel set of targets. Both the Abd-B specific targets and the cofactor-dependent Ubx targets are in chromatin that is relatively DNase1 inaccessible prior to the expression of Hox proteins/Hox cofactors.

Conclusions

Our experiments demonstrate a strong role for chromatin accessibility in Hox protein binding and suggest that Hox protein competition with nucleosomes has a major role in Hox protein target specificity in vivo.

【 授权许可】

   
2016 Beh et al.

【 图 表 】

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