E2F Transcription Factors Control the Roller Coaster Ride of Cell Cycle Gene Expression

Abstract

Initially, the E2F transcription factor was discovered as a factor able to bind the adenovirus E2 promoter and activate viral genes. Afterwards it was shown that E2F also binds to promoters of nonviral genes such as C-MYC and DHFR, which were already known at that time to be important for cell growth and DNA metabolism, respectively. These findings provided the first clues that the E2F transcription factor might be an important regulator of the cell cycle. Since this initial discovery in 1987, several additional E2F family members have been identified, and more than 100 targets genes have been shown to be directly regulated by E2Fs, the majority of these are important for controlling the cell cycle. The progression of a cell through the cell cycle is accompanied with the increased expression of a specific set of genes during one phase of the cell cycle and the decrease of the same set of genes during a later phase of the cell cycle. This roller coaster ride, or oscillation, of gene expression is essential for the proper progression through the cell cycle to allow accurate DNA replication and cell division. The E2F transcription factors have been shown to be critical for the temporal expression of the oscillating cell cycle genes. This review will focus on how the oscillation of E2Fs and their targets is regulated by transcriptional, post-transcriptional and post-translational mechanism in mammals, yeast, flies, and worms. Furthermore, we will discuss the functional impact of E2Fs on the cell cycle progression and outline the consequences when E2F expression is disturbed.

Cord blood DNA methylome in newborns later diagnosed with autism spectrum disorder reflects early dysregulation of neurodevelopmental and X-linked genes

“…Similar patterns were observed regardless of the direction of methylation change or tissue type. Additionally, only female X-linked ASD DMRs were enriched for the E2F1, E2F4, and E2F6 transcription factors, which are all expressed in fetal brain, sensitive to methylation, and regulate cell cycle progression [53]. The disruption of active regulatory regions in females can also be seen in the large number of replicated X chromosome DMR genes in females compared to males, including MECP2, which was previously found to have altered methylation in female ASD brain [54].…”

Cell cycle oscillators underlying orderly proteolysis of E2F8

“…The E2F family of transcription factors plays a pivotal role in regulating pro-and anti-44 proliferative processes, with implications in tissue homeostasis and human disease, most 45 notably cancer (Chen, Tsai et al, 2009). E2F1, the canonical member of the E2F family, is at 46 the crossroads of the cell cycle and cell death, triggering the gene program dictating S-phase 47 and mitotic entry on the one hand, and, on the other hand, apoptosis (Hallstrom & Nevins,48 2009, Polager & Ginsberg, 2008, Thurlings & de Bruin, 2016. 49…”

Loss of ENT1 increases cell proliferation in the annulus fibrosus of the intervertebral disc

“…Of note, the most upregulated genes in ENT1 −/− AF tissues compared with WT at both 2 and 6 months of age included numerous immunoglobulin heavy chain or κ variable region transcripts. In the context of the current study, we do not have an explanation for the large fold-changes in these genes; however, they may reflect cellular processes not directly (Polager & Ginsberg, 2009;Thurlings & de Bruin, 2016). Importantly, the activity of E2f family members is directly modulated by complex formation with retinoblastoma protein family members (Rb1, Rbl1, and p130) (Thurlings & de Bruin, 2016).…”