Variable Requirements for DNA-Binding Proteins at Polycomb-Dependent Repressive Regions in Human HOX Clusters
Autor: | Caroline J. Woo, Peter V. Kharchenko, Laurence Daheron, Peter J. Park, Robert E. Kingston |
---|---|
Rok vydání: | 2013 |
Předmět: |
animal structures
genetic structures Transcription Genetic Polycomb-Group Proteins macromolecular substances Cell fate determination Biology DNA-binding protein Polycomb-group proteins SUZ12 Animals Humans Regulatory Elements Transcriptional Hox gene Molecular Biology Psychological repression Cells Cultured Homeodomain Proteins Genetics YY1 fungi Genes Homeobox Polycomb Repressive Complex 2 Gene Expression Regulation Developmental Mesenchymal Stem Cells Articles Cell Biology DNA-Binding Proteins BMI1 Multigene Family |
Zdroj: | Molecular and Cellular Biology. 33:3274-3285 |
ISSN: | 1098-5549 |
DOI: | 10.1128/mcb.00275-13 |
Popis: | Polycomb group (PcG)-mediated repression is an evolutionarily conserved process critical for cell fate determination and maintenance of gene expression during embryonic development. However, the mechanisms underlying PcG recruitment in mammals remain unclear since few regulatory sites have been identified. We report two novel prospective PcG-dependent regulatory elements within the human HOXB and HOXC clusters and compare their repressive activities to a previously identified element in the HOXD cluster. These regions recruited the PcG proteins BMI1 and SUZ12 to a reporter construct in mesenchymal stem cells and conferred repression that was dependent upon PcG expression. Furthermore, we examined the potential of two DNA-binding proteins, JARID2 and YY1, to regulate PcG activity at these three elements. JARID2 has differential requirements, whereas YY1 appears to be required for repressive activity at all 3 sites. We conclude that distinct elements of the mammalian HOX clusters can recruit components of the PcG complexes and confer repression, similar to what has been seen in Drosophila. These elements, however, have diverse requirements for binding factors, which, combined with previous data on other loci, speaks to the complexity of PcG targeting in mammals. |
Databáze: | OpenAIRE |
Externí odkaz: |