Testis-specific transcription mechanisms promoting male germ-cell differentiation

Abstract

Male germ-cell differentiation requires spermatogenic stage-and cell-specific gene expression that is achieved by unique chromatin remodeling, transcriptional control and the expression of testis-specific genes or isoforms. Recent findings have shown that the testis has specialized transcription complexes that coordinate the differentiation program of spermatogenesis. There are male germ cell-specific differences in the components of the general transcription machinery. These include upregulated expression of the TATA-binding protein (TBP) family and its associated cofactors. Importantly, a member of the TBP family, TBP-like factor (TLF), has a distribution pattern that is dependent on the spermatogenic cycle and is essential for spermatogenesis. Interestingly TBP-associated factor (TAF7), a factor of the transcription factor (TF)IID complex, is exchanged at a critical stage in germ cell development for the testis-specific paralogue TAF7L. A compelling amount of data has established that cAMP-response-element modulator (CREM), a transcription factor responsive to the cAMP signal transduction pathway, drives expression of key testis-specific genes. In this review we summarize recent advances in the transcription machinery that is testis-specific, gene-selective and necessary for the process of spermatogenesis.

A novel nucleocytoplasmic shuttling sequence of DAZAP1, a testis-abundant RNA-binding protein

“…This is consistent with the observation that DAZAP1 is found in the cytoplasm of elongating spermatids when the nuclear transcription is turning off (Vera et al 2002). Additional proteins that are involved in the regulation of transcription, such as ACT (activator of CREM in the testis) and the spermatidexpressed kinesin KIF17b, also relocate from the nucleus to the cytoplasm in elongating spermatids (Kimmins et al 2004;Hogarth et al 2005). The mechanisms underlying the cytoplasmic accumulation of DAZAP1 during transcription inhibition in somatic cells and at spermatid elongation in the testis could be different, however.…”

DNA Methylation-dependent Modulator of Gsg2/Haspin Gene Expression

“…Tokuhiro et al defined a 193-bp genomic interval containing the TSS of Gsg2 as a minimal promoter by demonstrating that a transgenic reporter driven by the 193-bp fragment mimics the endogenous expression patterns of Gsg2 in testicular germ cells [20]. They also found that the testicular germ cell nuclear factor(s) specifically binds to the minimal promoter sequence [20], although the minimal promoter does not contain the binding sites of the testis-specific isoforms of transcription factors such as general transcription factor IIA 1-like and cAMP-responsive element modulator tau, which are known to be responsible for the high level expression of certain genes in spermatogenic cells [28,29]. Thus, the expression pattern of Gsg2 in spermatogenic cells may be governed by the minimal promoter and its germ cell-specific binding factors.…”

An association between sperm PLCζ levels and varicocele?

“…A study of background literature using quantitative PCR or microarray analysis reveals that testis-specific genes or genes with enhanced expression in the testis, such as HSPA2, SPAG11, protamines 1 and 2, MTIM, PHLDA1, [31,35]. One reason for this altered expression might be related to common transcription factors, such as CREM required for the expression of these genes during spermatogenesis [35,36]. In regard to this, Kimmins et al stated that CREM knockout mice are infertile and spermatogenesis is arrested at round spermatid stage.…”

“…In regard to this, Kimmins et al stated that CREM knockout mice are infertile and spermatogenesis is arrested at round spermatid stage. They concluded that Binfertility in these mice is attributed to the lack of expression of key post-meiotic genes required for differentiation such as protamine 1 and 2, transition proteins 1 and 2, proacrosin and calspermin among others^ [36]. Therefore, reduced expression of PLCζ could be the consequence of a similar phenomenon.…”