Rimokh et al. (1991) cloned the breakpoint of a t(8;12) chromosomal translocation in a case of B-cell chronic
lymphocytic leukemia and isolated a coding sequence mapping on 12q22. This sequence detected a 1.8-kb transcript in
virtually all tissues tested except in the brain and muscle where the signal was barely detectable. The putative gene
corresponding to this sequence, termed BTG1 for B-cell translocation gene 1, was shown to be highly conserved in
evolution.
NCBI Summary:
This gene is a member of an anti-proliferative gene family that regulates cell growth and differentiation. Expression of this gene is highest in the G0/G1 phases of the cell cycle and downregulated when cells progressed through G1. The encoded protein interacts with several nuclear receptors, and functions as a coactivator of cell differentiation. This locus has been shown to be involved in a t(8;12)(q24;q22) chromosomal translocation in a case of B-cell chronic lymphocytic leukemia. [provided by RefSeq, Oct 2008]
General function
Cell proliferation
Comment
CO-transcriptional factor
Cellular localization
Cytoplasmic, Nuclear
Comment
Ovarian function
Luteinization, Early embryo development
Comment
BTG4 is a meiotic cell cycle-coupled maternal-zygotic-transition licensing factor in oocytes. Yu C et al. (2017) The mRNAs stored in oocytes undergo general decay during the maternal-zygotic transition (MZT), and their stability is tightly interconnected with meiotic cell-cycle progression. However, the factors that trigger decay of maternal mRNA and couple this event to oocyte meiotic maturation remain elusive. Here, we identified B-cell translocation gene-4 (BTG4) as an MZT licensing factor in mice. BTG4 bridged CNOT7, a catalytic subunit of the CCR4-NOT deadenylase, to eIF4E, a key translation initiation factor, and facilitated decay of maternal mRNA. Btg4-null females produced morphologically normal oocytes but were infertile, owing to early developmental arrest. The intrinsic MAP kinase cascade in oocytes triggered translation of Btg4 mRNA stored in fully grown oocytes by targeting the 3' untranslated region, thereby coupling CCR4-NOT deadenylase-mediated decay of maternal mRNA with oocyte maturation and fertilization. This is a key step in oocyte cytoplasmic maturation that determines the developmental potential of mammalian embryos.//////////////////
Expression regulated by
LH
Comment
Rapid effects of luteinizing hormone on gene expression in the mural granulosa cells of mouse periovulatory follicles. Carletti M et al. Luteinizing hormone (LH) acts on periovulatory granulosa cells by activating the PKA pathway as well as other cell signaling cascades to increase the transcription of specific genes necessary for ovulation and luteinization. Collectively, these cell signaling responses occur rapidly (within minutes), however, presently no high throughput studies have reported changes before 4 h after the LH surge. To identify early response genes that are likely critical for initiation of ovulation and luteinization, mouse granulosa cells were collected before and 1 h after hCG. Fifty-seven gene transcripts were significantly (p<0.05) upregulated and 3 downregulated following hCG. Twenty-four of these transcripts were known to be expressed after the LH/hCG surge at later time points, while 36 were unknown to be expressed by periovulatory granulosa cells. Temporal expression of several transcripts, including the transcription factors Nr4a1, Nr4a2, Egr1, Egr2, Btg1, and Btg2, and the EGF-like ligands Areg and Ereg, were analyzed by quantitative RT-PCR, and their putative roles in granulosa cell function are discussed. Epigen (Epgn), another member of the family of EGF-like ligands, was identified for the first time in granulosa cells as rapidly induced by LH/hCG. We demonstrate that Epgn initiates cumulus expansion, similar to the other EGF-receptor ligands Areg and Ereg. These studies illustrate that a number of changes in gene expression occur in vivo in response to LH, and that many of the differentially expressed genes are transcription factors that we would predict in turn modulate granulosa cell gene expression to ultimately impact the processes of ovulation and luteinization.
Ovarian localization
Oocyte, Granulosa, Theca
Comment
The B Cell Translocation Gene (BTG) Family in the Rat Ovary: Hormonal Induction, Regulation, and Impact on Cell Cycle Kinetics. Li F et al. The B Cell Translocation Gene (BTG) family regulates gene transcription, cellular differentiation, and inhibits proliferation. The present study investigated the spatiotemporal expression pattern of BTG members and their potential role in the rat ovary during the periovulatory period. Immature female rats (22-23 days old) were injected with PMSG to stimulate follicular development. Ovaries or granulosa cells were collected at various times after hCG administration (n=3/time point). Real-time PCR analysis revealed that mRNA for Btg1, Btg2, and Btg3 were highly induced both in intact ovaries and granulosa cells by 4 to 8 h after hCG treatment although their temporal expression patterns differed. In situ hybridization analysis demonstrated that Btg1 mRNA expression was highly induced in theca cells at 4 h after hCG, primarily localized to granulosa cells at 8 h, and decreased at 24 h. Btg2 and Btg3 mRNA was also induced in granulosa cells, however, Btg2 mRNA was observed in newly forming corpora lutea. Inhibition of progesterone action and the EGF pathway did not change Btg1 and Btg2 mRNA expression, whereas inhibition of prostaglandin synthesis or RUNX activity diminished Btg2 mRNA levels. Overexpression of BTG1 or BTG2 arrested granulosa cells at the G0/G1 phase of the cell cycle and decreased cell apoptosis. In summary, hCG induced Btg1, Btg2 and Btg3 mRNA expression predominately in the granulosa cell compartment. Our findings suggest that the induction of the BTG family may be important for theca and granulosa cell differentiation into luteal cells by arresting cell cycle progression.