CREM: A Transcriptional Master Switch Governing the cAMP Response in the Testis

Monaco, Lucía; Nantel, F.; Foulkes, Nicholas S.; Sassone–Corsi, Paolo

doi:10.1007/978-3-662-03230-5_5

Cited by 14 publications

(6 citation statements)

References 71 publications

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“…As a number of transcripts encoding proteins essential for spermatogenesis are alternatively processed in the testis, such as CREM (28)(29)(30), RNA processing defects might therefore lead indirectly to spermatogenic defects. The RNAs to which RBM putatively binds may either not be restricted to specific stages of spermatogenesis, or RBM may have different target RNAs in different germ cell types.…”

Section: Resultsmentioning

confidence: 99%

Expression of RBM in the nuclei of human germ cells is dependent on a critical region of the Y chromosome long arm

Elliott

Millar

Oghene

et al. 1997

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

230

153

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The association of abnormal spermatogenesis in men with Y chromosome deletions suggests that genes important for spermatogenesis have been removed from these individuals. Recently, genes encoding two putative RNAbinding proteins (RBM and DAZ͞SPGY) have been mapped to two different regions of the human Y chromosome. Both of these genes encode proteins that contain a single RNA recognition motif and a (different) internally repeating sequence. Y-linked RBM homologues are found in all mammalian species. We have raised an antiserum to RBM and used it to show that RBM is a nuclear protein expressed in fetal, prepubertal, and adult male germ cells. The distribution of RBM protein in the adult correlates with the pattern of transcriptional activity in spermatogenesis, suggesting that RBM is involved in the nuclear metabolism of newly synthesized RNA. RBM sequences are found on both arms of the Y chromosome making genotype-phenotype correlations difficult for this gene family. To address the location of the functional genes and the consequences of their deletion, we examined a panel of men with Y chromosome deletions and known testicular pathologies using this antiserum. This approach enabled us to map a region of the Y chromosome essential for RBM expression. In the absence of detectable RBM expression we see stages of germ cell development up to early meiosis, but not past this point into the haploid phase of spermatogenesis.

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Section: Resultsmentioning

confidence: 99%

Expression of RBM in the nuclei of human germ cells is dependent on a critical region of the Y chromosome long arm

Elliott

Millar

Oghene

et al. 1997

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

230

153

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“…CREM binds to CREs, suggesting that CREs could constitute down-stream targets of CREM. CREM modulates the transcription of cAMP-response genes, and regulates gene expression in spermatids Monaco et al 1996;Walker and Habener 1996). The CREM gene gives rise to both full-length activator proteins (CREMτα, CREMτ, CREMτ1, CREMτ2) and truncated repressor proteins (CREMα, CREMβ, CREMχ), generated by alternative exon splicing and alternative startsites for translation (Oliva and Dixon 1991;Delmas et al 1992Delmas et al , 1993Laoide et al 1993;Masquilier et al 1993;Kistler et al 1994;Walker et al 1994;Walker and Habener 1996).…”

Section: Cre-boxmentioning

confidence: 97%

Transcriptional and translational regulation of gene expression in haploid spermatids

Steger¹

1999

Anatomy and Embryology

273

164

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During spermiogenesis, round spermatids undergo complex morphological, biochemical, and physiological modifications resulting in the formation of mature spermatozoa. While in round spermatids histones and non-histone proteins are replaced by transition proteins, in elongating spermatids, transition proteins are removed from the condensing chromatin and are replaced by protamines, which are the principal basic nuclear proteins of mature spermatozoa. The tightly packed DNA-protamine complexes cease transcription several days before the completion of spermiogenesis. Thus, major modifications in both nuclear and cytoplasmic structures continue throughout spermiogenesis, stringent temporal and stage-specific gene expression is a prerequisite for the correct differentiation of round spermatids into mature spermatozoa. The genes for transition proteins and protamines are transcribed in round and elongating spermatids. Transcription is regulated via methylation and trans-acting factors that bind to the TATA-box, the CRE-box, or other specific DNA sequences in the promoter region. The transcripts are stored as ribonucleoprotein particles in a translationally repressed state for several days and are translated in elongating and elongated spermatids. It has been demonstrated that, in haploid spermatids, essentially every mRNA exhibits evidence of translational repression. Translational regulation involves protein repressors that bind to the poly-A tail or specific RNA sequences located in the 3'-UTR.

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“…Recently, many leucine zipper proteins have been reported and revealed to play key roles in cell growth and differentiation (39). In haploid germ cells, a specific cAMP response element modulatory protein (CREM) is believed to control some gene expression (40,41). Haspin may associate with such a factor to play a regulatory role in haploid-specific gene expression.…”

Section: Ectopic Expression Of Haspin Inhibits Proliferation Of Hek-2mentioning

confidence: 99%

Identification and Characterization of a Haploid Germ Cell-specific Nuclear ProteinKinase (Haspin) in Spermatid Nuclei and Its Effects on Somatic Cells

Tanaka¹,

Yoshimura²,

Nozaki³

et al. 1999

Journal of Biological Chemistry

110

111

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We have cloned the entire coding region of a mouse germ cell-specific cDNA encoding a unique protein kinase whose catalytic domain contains only three consensus subdomains (I-III) instead of the normal 12. The protein possesses intrinsic Ser/Thr kinase activity and is exclusively expressed in haploid germ cells, localizing only in their nuclei, and was thus named Haspin (for haploid germ cell-specific nuclear protein kinase). Western blot analysis showed that specific antibodies recognized a protein of M r 83,000 in the testis. Ectopically expressed Haspin was detected exclusively in the nuclei of cultured somatic cells. Even in the absence of kinase activity, however, Haspin caused cell cycle arrest at G 1 , resulting in growth arrest of the transfected somatic cells. In a DNA binding experiment, approximately onehalf of wild-type Haspin was able to bind to a DNAcellulose column, whereas the other half was not. In contrast, all of the deletion mutant Haspin that lacked autophosphorylation bound to the DNA column. Thus, the DNA-binding activity of Haspin may, in some way, be associated with its kinase activity. These observations suggest that Haspin has some critical roles in cell cycle cessation and differentiation of haploid germ cells.

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CREM: A Transcriptional Master Switch Governing the cAMP Response in the Testis

Cited by 14 publications

References 71 publications

Expression of RBM in the nuclei of human germ cells is dependent on a critical region of the Y chromosome long arm

Expression of RBM in the nuclei of human germ cells is dependent on a critical region of the Y chromosome long arm

Transcriptional and translational regulation of gene expression in haploid spermatids

Identification and Characterization of a Haploid Germ Cell-specific Nuclear ProteinKinase (Haspin) in Spermatid Nuclei and Its Effects on Somatic Cells

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