Fig. 2: Regulatory mechanisms to control transposable elements.
From: Transposable elements as genome regulators in normal and malignant haematopoiesis
Various transcriptional and post-transcriptional mechanisms control the activity of TEs. Epigenetic repression of TEs is primarily achieved through the sequence-specific recognition of TE elements by KRAB-Zinc Finger Proteins (KRAB-ZFPs). These proteins recruit the KAP1 cofactor, which, in turn, facilitates the formation of a repressive chromatin structure by recruiting histone modifying enzymes, such as SETDB1 and histone deacetylase (HDAC), leading to histone methylation and deacetylation. DNA methyltransferases (DNMTs) deposit repressive DNA cytosine methylation marks on TE sequences, further silencing their activity. The maintenance of this silencing is supported by DNA methylation maintenance mechanisms during replication, primarily involving DNMT1 and UHRF1. Additionally, the human silencing hub (HUSH) complex targets young TE families and recruits SETDB1 to silence target TEs. Moreover, RNA modifications, including m6A and m5C, influence TE transcript stability, splicing, and translation, adding an additional layer of regulation. Created in BioRender.
