演題詳細

一般口演 / Oral Session

一般口演 18 (Oral Session 18) :エピジェネティクス

print

日程
2013年10月11日(金)
時間
15:25 - 16:25
会場
第3会場 / Room No.3 (さっぽろ芸文館 3F 蓬莱)
座長・司会
瀧原 義宏 (Yoshihiro Takihara):1
1:広島大学原爆放射線医科学研究所 幹細胞機能学研究分野
 
前へ戻る

The histone methyltransferase Eset is required for the maintenance of hematopoietic stem cells

演題番号 : OS-1-91

小出 周平 (Shuhei Koide):1、宮城 聡 (Satoru Miyagi):1、George Wendt:1、大島 基彦 (Motohiko Oshima):1,2、岩間 厚志 (Atsushi Iwama):1

1:Cell Moll Med., Chiba Univ., Japan、2:JST, CREST, Tokyo, Japan

 

Covalent modifications of histone tails play important roles in gene transcription and silencing. Methylation of Histone H3 at Lysine 9 (H3K9) mediates heterochromatin formation by forming a binding site for HP1. ERG-associated protein with a SET domain (ESET) or SETDB1 is an H3K9-specific tri-methyltransferase in the euchromatic region. In mice, homozygous mutations of Eset results in peri-implantation lethality between 3.5 and 5.5 days postcoitum. However, its role in hematopoiesis remains to be addressed. In this study, we performed detailed analyses of mice in which Eset was deleted only in adult bone marrow (BM) hematopoietic cells. Interestingly, we observed that Lin-Sca-1+c-kit+ (LSK) hematopoietic stem/progenitor cells (HSPCs) are progressively depleted upon loss of Eset and the mice showed transient extramedullary hematopoiesis in the spleen, suggesting egression of HSPCs from the BM. Competitive BM repopulating assays revealed severely impaired repopulating capacity of Eset-deficient HSCs. Gene expression profiling of LSK HSPCs by microarray analysis revealed that quite different sets of genes are altered in expression by loss of Eset compared to those by loss of polycomb-group repressive histone modifiers. These results indicate that Eset plays an essential role in maintenance of hematopoiesis in BM via regulating its unique target genes. We are now working on the mechanistic aspects of Eset in the regulation of HSPCs.

前へ戻る