The expanding family of CREB/CREM transcription factors that are involved with spermatogenesis

Don, Jeremy; Stelzer, Gil

doi:10.1016/s0303-7207(01)00696-7

Cited by 173 publications

(115 citation statements)

References 33 publications

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“…Crem is a transcriptional factor that is phosphorylated and activated by the cAMP-regulated protein kinase A (32,33). In germ cells of sexually mature male rodents, cAMP levels are largely dependent on the activity of the two splice variants of sAC (8), which is directly regulated by bicarbonate ions (7,8).…”

Section: Discussionmentioning

confidence: 99%

Anion exchanger 2 is essential for spermiogenesis in mice

Medina

Recalde

Prieto

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Na ؉ -independent anion exchangers (AE) mediate electroneutral exchange of Cl ؊ for HCO 3 ؊ ions across cell membranes, being involved in intracellular pH and cell volume regulation and in transepithelial hydroionic fluxes. Bicarbonate activation of adenylyl cyclase is known to be necessary for sperm motility and sperm capacitation, and a few studies have suggested a possible role of AE carriers in reproduction. Among the four AE genes identified in mammals thus far, only Ae2 (Slc4a2) has been determined to be expressed in the male reproductive system, especially in developing spermatozoa and in epididymal epithelium. Most AE genes drive alternative transcription, which in mouse Ae2 results in several Ae2 isoforms. Here, we generated mice carrying a targeted disruption of Ae2 that prevents the expression of the three AE2 isoforms (Ae2a, Ae2b1, and Ae2b2) normally found in mouse testes. Male Ae2 ؊/؊ mice (but not female Ae2 ؊/؊ mice) are infertile. Histopathological analysis of Ae2 ؊/؊ testes shows an interruption of spermiogenesis, with only a few late spermatids and a complete absence of spermatozoa in the seminiferous tubules. The number of apoptotic bodies is increased in the seminiferous tubules and in the epididymis, which also shows squamous metaplasia of the epididymal epithelium. Our findings reveal an essential role of Ae2 in mouse spermiogenesis and stress the recently postulated involvement of bicarbonate in germ-cell differentiation through the bicarbonate-sensitive soluble-adenylyl-cyclase pathway.

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Section: Discussionmentioning

confidence: 99%

Anion exchanger 2 is essential for spermiogenesis in mice

Medina

Recalde

Prieto

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Together with the cAMP response element binding protein (CREB), CREM is a member of the ATF superfamily of transcription factors. This family is involved in numerous physiological processes, including immune homeostasis, steroid metabolism, and spermatogenesis (9,10). As a result of its specific exon composition, CREM exerts both trans-activating and trans-repressing effects on target genes.…”

Section: Inflammation | Gene Regulationmentioning

confidence: 99%

“…CREMα has been linked to reduced IL-2 and increased IL-17A expression through diametric trans-regulatory effects on the IL2 and IL17A genes (8,(15)(16)(17). CREMα expression is controlled by trans-activation and trans-repression of the CREM promoter P1 (9,10). In SLE patients, dephosphorylated Sp-1 trans-activates CREM P1 in a disease activity-dependent manner (10,12).…”

Section: Inflammation | Gene Regulationmentioning

confidence: 99%

cAMP response element modulator α controls IL2 and IL17A expression during CD4 lineage commitment and subset distribution in lupus

Hedrich

Crispín

Rauen

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

119

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Appropriate expression of IL-2 plays a central role during the priming and differentiation of T cells. A tight balance between IL-2 and the effector cytokine IL-17A is essential for immune homeostasis. Epigenetic mechanisms have been documented as a key component of cytokine regulation during lineage commitment. The molecular mechanisms that induce chromatin remodeling are less well understood. We investigated epigenetic regulators that mediate the diametric expression of IL-2 and IL-17A in naive, central memory, and effector memory CD4 + T cells. We demonstrate that cAMP response modulator (CREM)α contributes to epigenetic remodeling of IL2 in effector memory T cells through the recruitment of DNMT3a. CREMα also reduces CpG-DNA methylation of the IL17A promoter. CREMα expression is regulated at the epigenetic level by CpG-DNA methylation, which allows increased CREMα expression in effector memory CD4 + T cells. T cells from patients with systemic lupus erythematosus (SLE) express increased levels of CREMα and exhibit a phenotype that is similar to effector memory CD4 + T cells with epigenetically predetermined expression patterns of IL-2 and IL-17A. We conclude that CREMα mediates epigenetic remodeling of the IL2 and IL17A gene during T-cell differentiation in favor of effector memory T cells in health and disease.inflammation | gene regulation

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“…TSSK3 presents exclusively in and may function in Leydig cells [8,13]. TSSK4 phosphorylates the cAMP responsive element binding protein, which is important for germ cell differentiation [10,14]. Our previous study proposed that some single-nucleotide polymorphisms (SNPs) of TSSK4 may contribute to the susceptibility to idiopathic spermatogenic impairment [15].…”

Section: Introductionmentioning

confidence: 99%