A POP-1 repressor complex restricts inappropriate cell type-specific gene transcription during Caenorhabditis elegans embryogenesis.
In Caenorhabditis elegans, histone acetyltransferase CBP-1 counteracts the repressive activity of the histone deacetylase HDA-1 to allow endoderm differentiation, which is specified by the E cell. In the sister MS cell, the endoderm fate is prevented by the action of an HMG box-containing protein, POP-1, through an unknown mechanism. In this study, we show that CBP-1, HDA-1 and POP-1 converge on end-1, an initial endoderm-determining gene. In the E lineage, an essential function of CBP-1 appears to be the activation of end-1 transcription. We further identify a molecular mechanism for the endoderm-suppressive effect of POP-1 in the MS lineage by demonstrating that POP-1 functions as a transcriptional repressor that inhibits inappropriate end-1 transcription. We provide evidence that POP-1 represses transcription via the recruitment of HDA-1 and UNC-37, the C.elegans homolog of the co-repressor Groucho. These findings demonstrate the importance of the interplay between acetyltransferases and deacetylases in the regulation of a critical cell fate-determining gene during development. Furthermore, they identify a strategy by which concerted actions of histone deacetylases and other co-repressors ensure maximal repression of inappropriate cell type-specific gene transcription.
Calvo
D
D
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Victor
M
M
Gay
F
F
Sui
G
G
Luke
M P
MP
Dufourcq
P
P
Wen
G
G
Maduro
M
M
Rothman
J
J
Shi
Y
Y
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins / Q000502:physiology*; D050980:GATA Transcription Factors; D015801:Helminth Proteins / Q000502:physiology*; D006609:High Mobility Group Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C109211:END-1 protein, C elegans; D050980:GATA Transcription Factors; D015801:Helminth Proteins; D006609:High Mobility Group Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C096787:pop-1 protein, C elegans; C106184:unc-37 protein, C elegans