Unique aspects of transcription regulation in male germ cells

Abstract

Spermatogenesis is a complex and ordered differentiation process in which the spermatogonial stem cell population gives rise to primary spermatocytes that undergo two successive meiotic divisions followed by a major biochemical and structural reorganization of the haploid cells to generate mature elongate spermatids. The transcriptional regulatory programs that orchestrate this process have been intensively studied in model organisms such as Drosophila melanogaster and mouse. Genetic and biochemical approaches have identified the factors involved and revealed mechanisms of action that are unique to male germ cells. In a well-studied example, cofactors and pathways distinct from those used in somatic tissues mediate the action of CREM in male germ cells. But perhaps the most striking feature concerns the paralogs of somatically expressed transcription factors and of components of the general transcription machinery that act in distinct regulatory mechanisms in both Drosophila and murine spermatogenesis.

Figure 1.

Schematic description of TFIID complexes that are involved in transcription in Drosophila and murine male germ cells. The structure of TFIID as determined from immunoelectron microscopy (EM) experiments is shown on the left of the figure. The TBP and TAF subunits are represented by colored balls superimposed on the reconstructed EM model. Drosophila spermatocytes express paralogs of several TAFs that are shown organized in the form of a partial TFIID complex. The heterodimerization partners of mia and sa remain to be determined along with the presence of TAFs 2, 7, 11, and 13 in this complex. These spermatocytes likely also contain a TFIID complex comprising somatically expressed TAFs and the TRF2 complex. Murine spermatocytes predominantly contain a normal TFIID complex containing TAF4 and/or TAF4b. In haploid cells, TAF4 is strongly down-regulated leading to loss of full TFIID and accumulation of the TBP-TAF1-TAF7L submodule. TBP can interact with either TFIIA or ALF to mediate elevated levels of mRNA transcription in these cells. TRF2 also interacts with either TFIIA or ALF and may mediate transcription of a subset of essential genes or it may interact with chromatin via TIPT and HP1γ.

Figure 2.

Schematic model of the CREM-ACT-KIF17b regulatory pathway. (A) In somatic cells, CREB and CREM activate transcription following phosphorylation of a conserved serine residue and recruitment of the CBP and p300 coactivators. CREB and CREM can also interact with TAF4 that is required as a coactivator for their activity. Alternatively, CREB can also activate transcription independent of CBP/p300 via the TORC coactivators. (B) In germ cells, CREM interacts with ACT. At the elongation phase ACT is exported to the cytoplasm by KIF17B to repress CREM activation of target genes. KIF17B also transports mRNAs to the chromatoid body where it interacts with the MIWI protein. Phosphorylation of KIF17B by PKA increases its cytoplasmic localization.