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Additional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets.

Hsiao-Lei Lai¹, Q Tian Wang

¹Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.

|September 17, 2013

Summary

ASXL2 protein is crucial for heart function by regulating gene expression. It works with PRC2 to maintain repressive histone marks, ensuring proper cardiac gene silencing.

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Area of Science:

Epigenetics
Molecular Biology
Cardiovascular Biology

Background:

Polycomb Group (PcG) proteins are key epigenetic repressors.
The mechanism of gene repression by Asx family proteins, including ASXL2, is not fully understood.
ASXL2 is vital for mammalian heart function and influences H3K27me3 levels.

Purpose of the Study:

To identify ASXL2 target genes in the heart.
To elucidate the mechanism by which ASXL2 mediates gene repression.
To understand ASXL2's role in Polycomb Repressive Complex 2 (PRC2) activity.

Main Methods:

Identification of ASXL2 target genes in the heart.
Analysis of histone modifications (H3K27me2, H3K27me3, H2A ubiquitination) in Asxl2-deficient hearts.
Co-immunoprecipitation and co-localization studies to assess ASXL2 and PRC2 interaction and promoter binding.

Main Results:

ASXL2 deficiency impairs the conversion of H3K27me2 to H3K27me3 and removal of H2A monoubiquitination.
ASXL2 interacts with PRC2 in the adult heart and co-localizes to target gene promoters.
ASXL2 is essential for PRC2 binding and H3K27me3 enrichment at target promoters.

Conclusions:

ASXL2 plays a critical role in facilitating PRC2-mediated gene repression in the heart.
ASXL2's function involves regulating histone modification dynamics and PRC2 recruitment.
These findings provide new insights into the regulatory mechanisms of PcG proteins and gene silencing.