Exchange of GATA factors mediates transitions in looped chromatin organization at a developmentally regulated gene locus (Mol Cell, 2008, 29:232-242)

報告日期: 2008/11/25
報告時間: 15:10/16:00
報告學生: 陳玉霖
講評老師: 陳炳焜
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971125-1.pdf

Exchange of GATA Factors Mediates Transitions in Looped Chromatin Organization at a Developmentally Regulated Gene Locus

 

Huie Jing, Christopher R. Vakoc, Lei Ying, Sean Mandat, Hongxin Wang,  Xingwu Zheng, and Gerd A. Blobel

Molecular Cell, 2008, 29:232-242

 

Student: 陳玉霖

Commentator: 陳炳焜 老師

Time: 2008/11/25 15:10PM

Place: 602 教室

 

Factors controlling the direction of hematopoietic progenitor cell differentiation have been an important area of research. During differentiation, hematopoietic stem cells progressively loss self-renew capacity, while specific surface marker expression of mature blood cells is enhanced. GATA family proteins are involved in these differentiation processes. GATA-1 is expressed in mature and terminal differentiation cells, whereas GATA-2 is critical for maintenance and proliferation of the hematopoietic progenitor cells. Both GATA-1 and GATA-2 are regulated antagonistically during erythroid differentiation. GATA-1 represses GATA-2 expression. However, GATA-2 activates the expression of GATA-1. Moreover, GATA also interacts with other cofactors, such as FOG-1 and EKCF during erythroid differentiation. Previously, it is found that these factors formed a regulation complex that is in chromatin loops between Kit gene enhancer and promoter. These chromatin loops have been correlated with Kit gene activation. However, whether these chromatin loops are reconfigured when Kit gene is turned off remains unclear. The authors analyzed the 310 kb locus occupied by GATA-1, GATA-2, polymerase II and histone acetylation. Using capturing chromosome conformation (3C) technique, they found that GATA-2 binds at -114 kb element as an enhancer and forms a loop with the promoter-proximal region. When GATA-1 is activated, GATA-2 is displaced and the loop of enhancer promoter was disruption. Interestingly, the newly formed loop at promoter-downstream is actually the GATA-1 binding elements. This study shows that transcription factor–dependent dynamic reconfiguration of the long-range enhancer-promoter interaction is important in differentiation control and explains how these stage specific transcription factors can modulate differential progression.

 

Reference:

1. Vakoc, C.R., Letting, D.L., Gheldof, N., Sawado, T., Bender, M.A., Groudine, M., Weiss, M.J., Dekker, J., and Blobel, G.A. (2005). Proximity among distant regulatory elements at the beta-globin locus requires GATA-1 and FOG-1. Mol. Cell 17, 453–462.

2. Dekker, J., Rippe, K., Dekker, M., and Kleckner, N. (2002). Capturing chromosome conformation. Science 295, 1306–1311.

3. Osborne, C.S., Chakalova, L., Brown, K.E., Carter, D., Horton, A., Debrand, E., Goyenechea, B., Mitchell, J.A., Lopes, S., Reik, W., and Fraser, P. (2004). Active genes dynamically colocalize to shared sites of ongoing transcription. Nat. Genet. 36, 1065–1071.