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Published on: March 31, 2019
Variable requirements for DNA-binding proteins at polycomb-dependent repressive regions in human HOX clusters
Caroline J Woo1, Peter V Kharchenko, Laurence Daheron
1Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Molecular and Cellular Biology
|June 19, 2013
Summary
Researchers identified novel Polycomb group (PcG) regulatory elements in human HOX clusters. These elements recruit PcG proteins to control gene expression, revealing complex targeting mechanisms in mammals.
Area of Science:
- Developmental Biology
- Epigenetics
- Genomics
Background:
- Polycomb group (PcG)-mediated repression is crucial for embryonic development and cell fate.
- Mechanisms of PcG recruitment in mammals are not fully understood due to limited identified regulatory sites.
Purpose of the Study:
- To identify and characterize novel PcG-dependent regulatory elements in human HOXB and HOXC clusters.
- To compare the repressive activities of these novel elements with a known element in the HOXD cluster.
- To investigate the roles of JARID2 and YY1 in regulating PcG activity at these elements.
Main Methods:
- Reporter construct assays in mesenchymal stem cells.
- Recruitment analysis of PcG proteins (BMI1, SUZ12).
- Assessment of PcG expression-dependent repression.
- Examination of DNA-binding protein (JARID2, YY1) involvement.
Main Results:
- Two novel PcG-dependent regulatory elements were identified in human HOXB and HOXC clusters.
- These elements, along with a HOXD element, recruited PcG proteins (BMI1, SUZ12) and conferred repression dependent on PcG expression.
- JARID2 showed differential requirements, while YY1 was essential for repression at all three HOX elements.
Conclusions:
- Distinct elements within mammalian HOX clusters can recruit PcG complexes and mediate gene repression.
- PcG targeting in mammals is complex, with varying requirements for DNA-binding factors like JARID2 and YY1 at different regulatory elements.
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