Developmental control and alternative splicing of the placentally expressed transcripts from the human growth hormone gene cluster.
Four of the five genes in the human growth hormone gene cluster are expressed in the villous layer of the placenta. We report that the expression of these genes, hCS-A, hCS-B, hCS-L, and hGH-V, are coordinately induced during fetal development, increasing between 12 and 20 weeks of gestation and then plateauing through term. Within the context of this coordinate activation, these genes are expressed at widely different levels and are alternatively spliced in different patterns. There is a developmentally regulated switch in the relative expression of the two chorionic somatomammotropin genes, hCS-A and hCS-B. Starting from approximately equal levels at 8 weeks of gestation, hCS-A is expressed 5-fold more abundantly than hCS-B by term. The proportion of alternatively spliced hGH-V transcripts that retain intron 4 is also developmentally regulated, increasing 3-fold during gestation to 15% at term. A small percentage of hCS transcripts stably retain intron 4 through gestation, the majority derived from the hCS-A gene. hCS-L transcripts undergo two distinct, developmentally stable, splicing pathways between exons 2 and 3. These result from the absence of the normal splice-donor site in intron 2 and the activation of two cryptic splice-acceptor sites. Despite high levels of sequence identity, the four placentally expressed genes in the growth hormone cluster generate a complex set of mRNAs based on alternative splicing and developmental regulation during gestation.
MacLeod
J N
JN
Department of Medicine, University of Pennsylvania, Philadelphia 19104-6144.
Lee
A K
AK
Liebhaber
S A
SA
Cooke
N E
NE
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D002824:Chorionic Villi / Q000502:physiology*; D003062:Codon / Q000235:genetics; D005314:Embryonic and Fetal Development; D005260:Female; D005333:Fetus / Q000502:physiology; D015723:Gene Library; D005865:Gestational Age; D013006:Growth Hormone / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D009838:Oligodeoxyribonucleotides; D010920:Placenta / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012326:RNA Splicing; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D003062:Codon; D009838:Oligodeoxyribonucleotides; D012313:RNA; D013006:Growth Hormone