SETting up the Epigenome Through the Histone Methyltransferase SETDB1
Zhuo Sun and Brian P. Chadwick
from: Epigenetics: Current Research and Emerging Trends (Edited by: Brian P. Chadwick). Caister Academic Press, U.K. (2015) Pages: 23-52.
Abstract
SETDB1 is unusual among the SET-domain containing histone methyltransferases (HMTases) due to the partitioning of its catalytic SET domain into two parts, hence its name "SET Domain Bifurcated 1". SETDB1 is one of several histone H3 lysine-9 HMTases, but is the only one that is essential in Drosophila. Through its ability to implement and maintain programmed silencing of genes that would otherwise interfere with differentiation and cell specialization, SETDB1 is indispensible for development from nematodes to mammals. In addition, SETDB1 is required to maintain pluripotency, in part through the silencing of endogenous retroviral elements that can act as promoters of chimeric transcripts or enhancers of surrounding genes when active. SETDB1 can be recruited to sites of action through a variety of proteins, among which targeting to KRAB-domain containing zinc finger proteins via the versatile adapter protein TRIpartite Motif-containing 28 (TRIM28) is best characterized. Through this large and diverse family of DNA binding proteins, TRIM28 guides SETDB1 to sites of action to shut down gene expression, which includes all silent alleles of known imprinted genes. SETDB1 is emerging as a key player in establishing and maintaining the epigenome. Due to this pivotal role, levels of SETDB1 protein needs to be strictly regulated to avoid it contributing to disease and cancer progression read more ...
