H2AZ is enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment (Cell, 2008, 135:649-661)

報告日期: 2009/05/19
報告時間: 15:10/16:00
報告學生: 許哲裕
講評老師: 王育民
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980519-1.pdf

H2AZ Is Enriched at Polycomb Complex Target Genes in ES Cells and Is Necessary for Lineage Commitment

 

 Creyghton MP, Markoulaki S, Levine SS, Hanna J, Lodato MA, Sha K, Young RA, Jaenisch R, Boyer LA.

 

Cell. 2008 Nov 14;135(4):649-61.

 

Speaker: 許哲裕

Commentator: 王育民 老師

Date: May 19, 2009. 15:10-16:00

Place: 602R

 

Abstract:

Elucidating how chromatin influences gene expression patterns and ultimately cell fate is fundamental to understand development and disease. Because of their distinctive ability to differentiate into multiple lineages, embryonic stem (ES) cells are a valuable model system for the study of changes in chromatin as a function of cell state. Chromatin structure is highly regulated by a variety of complex processes, that include ATP-dependent chromatin remodeling, posttranslational modifications of histones, and the replacement of conventional histones with specific variants. Many studies have shown that histone H2A variant H2AZ [1] incorporating can affect local histone modification patterns, the activity of chromatin remodeling enzymes, and chromatin conformation. Thus, the function of H2AZ appears to be highly context-dependent in a manner that influences transcriptional output.

To investigate the essential role of H2AZ during mammalian development, authors have generated genome-wide maps in ES cells, and found that H2AZ is enriched at a large set of silent developmental genes in a manner that is highly similar to that of the Polycomb group (PcG) protein [2] Suz12. Conversely, H2AZ enrichment was detected at active genes in multipotent neural precursors, suggesting that its dynamic redistribution is necessary for lineage specification. Together, these findings establish that H2AZ is necessary for execution of developmental programs but that it is dispensable for maintenance of the ES cell state. Collectively, this work suggests that the association between H2AZ and PcG proteins at target genes provides an important functional switch controlling the initial stages of lineage commitment.

 

References:

1.   Zlatanova J, Thakar A. (2008). H2A.Z: view from the top. Structure 16 (2): 166-79. Review.

2.   Schuettengruber, B., Chourrout, D., Vervoort, M., Leblanc, B., and Cavalli, G. (2007). Genome regulation by polycomb and trithorax proteins. Cell 128 (4): 735–45. Review.