An isoform of transcription factor CREM expressed during spermatogenesis lacks the phosphorylation domain and represses cAMP-induced transcription.
cAMP response element-binding protein (CREB) and modulator protein (CREM) regulate the transcription of cAMP-responsive genes via phosphorylation by cAMP-dependent protein kinase A. Reverse transcription and polymerase chain amplification of RNA from male germ cells identify an alternatively spliced CREM isoform, CREM delta C-G, lacking four exons including those encoding the protein kinase A-regulated phosphorylation domain and the flanking glutamine-rich transcriptional activation domains. CREM delta C-G retains exons that encode the basic-leucine zipper (bZIP) DNA-binding domain, binds to cAMP response elements (CREs), and competitively inhibits binding of CREB and CREM to CREs. Expression of CREM delta C-G inhibits transcription of a CRE-containing chloramphenicol acetyltransferase reporter plasmid induced by endogenous CREB. Antiserum to CREM detects CREM delta C-G in elongated spermatids from rat testis. These observations indicate that CREM delta C-G is a unique form of a competitive negative regulator of CREB-mediated gene transcription expressed in a maturation-dependent manner in haploid germ cells. The developmental specificity of CREM delta C-G suggests that it may play a role in transcriptional regulation during spermatogenesis.
Walker
W H
WH
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Harvard Medical School, Howard Hughes Medical Institute, Boston 02114.
Sanborn
B M
BM
Habener
J F
JF
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D000242:Cyclic AMP / Q000378:metabolism; D051786:Cyclic AMP Response Element Modulator; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005796:Genes; D008297:Male; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012097:Repressor Proteins; D013091:Spermatogenesis; D013737:Testis / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases