title: Roles of cofactors and chromatin accessibility in Hox protein target specificity.
abstract: 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.
authors.affiliation: Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Ching Yew
authors.initials: CY
authors.lastname: Beh
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY UK.
authors.forename: Sherif
authors.initials: S
authors.lastname: El-Sharnouby
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY UK.|Department of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH UK.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Chatzipli
authors.affiliation: Department of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH UK.|Cambridge Systems Biology Centre, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Russell
authors.affiliation: Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Siew Woh
authors.initials: SW
authors.lastname: Choo
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY UK.
authors.forename: Robert
authors.initials: R
authors.lastname: White
keywords: Chromatin accessibility; Hox proteins; Transcription factor