T-box factors: targeting to chromatin and interaction with the histone H3 N-terminal tail.
T-box transcription factors play a crucial role in development where they are implicated in patterning and cell fate decisions. Tbx2 and Tbx3 have also been implicated in several cancers including melanoma, and can act as antisenescence factors through their ability to repress p19(ARF) and p21(CIP1) expression. Although several target genes for T-box factors have been identified, it is unknown whether this family of proteins can bind chromatin, a property that would facilitate the epigenetic reprogramming that occurs in both development and cancer progression. Here, we show that Tbx2 has the potential to recognize mitotic chromatin in a DNA-dependent fashion, can interact specifically with the histone H3 N-terminal tail, a property shared with Tbx4, Tbx5 and Tbx6, and can also recognize nucleosomal DNA, with binding to nucleosomes being antagonized by the presence of the histone tails. Strikingly, in vivo Tbx2 co-localization with pericentric heterochromatin appears to be regulated and ectopic expression of Tbx2 leads to severe mitotic defects. Taken together our results suggest that Tbx2, and most likely other members of the T-box family, are able to target chromatin and may indicate a role for the T-box factors in epigenetic reprogramming events.
Demay
Florence
F
Signalling and Development Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey, UK.
Bilican
Bilada
B
Rodriguez
Mercedes
M
Carreira
Suzanne
S
Pontecorvi
Marco
M
Ling
Yan
Y
Goding
Colin R
CR
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D006367:HeLa Cells; D006570:Heterochromatin / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008938:Mitosis; D009707:Nucleosomes / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D020825:T-Box Domain Proteins / Q000378:metabolism*
D002843:Chromatin; D006570:Heterochromatin; D006657:Histones; D009707:Nucleosomes; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; D004247:DNA