Abstract
Yin Yang 1 (YY1) plays an indispensable role in embryonic development. YY1 contains an evolutionarily conserved, 22-amino acid segment, the PHO homology region (PHR), which is located within its central domain (spacer) and has been shown previously to participate in the recruitment of Polycomb group of proteins and in YY1-mediated transcription. In this report, we show that the PHR physically interacts with several Abd-B-type Hox proteins. Although ectopic expression of Hoxa11 enhanced target promoter activity, overexpression of YY1 repressed this effect, which was abrogated by YY1 siRNA and the histone deacetylase inhibitor trichostatin A. We have further demonstrated that this suppression effect was the result of YY1-dependent recruitment of HDAC2 to the Hoxa11 target promoter. Taken together, our findings show that YY1 represses Hoxa11-dependent transcription via interactions with the Hox proteins and HDAC recruitment, providing a link between an Abd-type Hox protein and a Polycomb group protein at the level of direct protein-protein interactions. These findings not only provide a novel insight into YY1 function but also identify a new regulation of homeotic protein-mediated transcriptional regulation in general.
Highlights
Polycomb group (PcG) proteins are transcriptional regulators essential for the establishment and maintenance of the transcriptionally silenced state of homeotic gene expression [7]
Yin Yang 1 (YY1) is evolutionarily conserved from Drosophila to human, the sequence homology between YY1 and PHO is limited to the DNA-binding zinc fingers and a 22-aa segment located at the central region of the protein (aa 205–226, PHO homology region (PHR)) [5]
We identified novel physical interactions between YY1 and the Abd-B-type Hox proteins and showed that the physical interactions are important for YY1 to negatively regulate Hox protein-dependent transcription in a manner that is dependent on the recruitment of histone deacetylases
Summary
Polycomb group (PcG) proteins are transcriptional regulators essential for the establishment and maintenance of the transcriptionally silenced state of homeotic gene expression [7]. It has been demonstrated that PHO binds a 17-base pair (bp) PRE sequence in the Drosophila engrailed gene [5] These early studies in Drosophila suggest an important role of YY1 in regulating homeotic gene transcription. We identified novel physical interactions between YY1 and the Abd-B-type Hox proteins and showed that the physical interactions are important for YY1 to negatively regulate Hox protein-dependent transcription in a manner that is dependent on the recruitment of histone deacetylases Taken together, these findings suggest that YY1 functions as a PcG protein to directly repress Hox gene transcription and participates in negatively regulating transcription mediated by the products of the Hox genes, i.e. via direct physical interactions of the homeodomain proteins. 2 The abbreviations used are: YY1, Yin Yang 1; cYY1, chicken YY1; PcG, Polycomb group; TSA, trichostatin A; X-gal, 5-bromo-4-chloro-3-indolyl--Dgalactopyranoside; -gal, -galactosidase; aa, amino acid(s); PHR, PHO homology region; HBS, Hox binding sequence; HA, hemagglutinin; GST, glutathione S-transferase; siRNA, small interfering RNA; HDAC, histone deacetylase Tel.: 617-432-4318; Fax: 617-432-6687; E-mail: yang_shi@hms. harvard.edu. 2 The abbreviations used are: YY1, Yin Yang 1; cYY1, chicken YY1; PcG, Polycomb group; TSA, trichostatin A; X-gal, 5-bromo-4-chloro-3-indolyl--Dgalactopyranoside; -gal, -galactosidase; aa, amino acid(s); PHR, PHO homology region; HBS, Hox binding sequence; HA, hemagglutinin; GST, glutathione S-transferase; siRNA, small interfering RNA; HDAC, histone deacetylase
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