ABSTRACT
The cleavage-stage (CS) histones of the sea urchin are known to be maternally expressed in the egg, have been implicated in chromatin remodeling of the male pronucleus following fertilization, and are the only histone variants present in embryonic chromatin up to the four-cell stage. With the help of partial peptide sequence information, we have isolated and identified CS H1, H2A, H2B, H3, and H4 cDNAs from egg poly(A)+ mRNA of the sea urchin Psammechinus miliaris. All five CS proteins correspond to replacement histone variants which are encoded by replication-independent genes containing introns, poly(A) addition signals, and long nontranslated sequences. Transcripts of the CS histone genes could be detected only during oogenesis and in development up to the early blastula stage. The CS proteins, with the exception of H4, are unique histones which are distantly related in sequence to the early, late, and sperm histone subtypes of the sea urchin. In contrast, the CS H1 protein displays highest sequence homology with the H1M (B4) histone of Xenopus laevis. Both H1 proteins are replacement histone variants with very similar developmental expression profiles in their respective species, thus indicating that the frog H1M (B4) gene is a vertebrate homolog of the CS H1 gene. These data furthermore suggest that the CS histones are of ancient evolutionary origin and may perform similar conserved functions during oogenesis and early development in different species.
Subject(s)
Gene Expression Regulation, Developmental , Histones/genetics , Sea Urchins/genetics , Xenopus laevis/genetics , Amino Acid Sequence , Animals , Base Sequence , DNA, Complementary/genetics , Egg Proteins/genetics , Embryo, Nonmammalian/chemistry , Female , Genes/genetics , Genetic Variation , Histones/analysis , Male , Molecular Sequence Data , Multigene Family/genetics , Oogenesis , RNA, Messenger/genetics , Sea Urchins/embryology , Sequence Homology, Amino Acid , Xenopus laevis/embryologyABSTRACT
Analyses of the human PAX-5 locus and of the 5' region of the mouse Pax-5 gene revealed that transcription from two distinct promoters results in splicing of two alternative 5' exons to the common coding sequences of exons 2-10. Transcription from the upstream promoter initiates downstream of a TATA box and occurs predominantly in B-lymphocytes, whereas the TATA-less downstream promoter is active in all Pax-5-expressing tissues. The human PAX-5 gene is located on chromosome 9 in region p13, which is involved in t(9;14)(pl3;q32) translocations recurring in small lymphocytic lymphomas of the plasmacytoid subtype and in derived large-cell lymphomas. A previous molecular analysis of a t(9;14) breakpoint from a diffuse large-cell lymphoma (KIS-1) demonstrated that the immunoglobulin heavy-chain (IgH) locus on 14q32 was juxtaposed to chromosome 9p13 sequences of unknown function [Ohno, H., Furukawa, T., Fukuhara, S., Zong, S. Q., Kamesaki, H., Shows, T. B., Le Beau, M. M., McKeithan, T. W., Kawakami, T. & Honjo, T. (1990) Proc. Natl. Acad. Sci. USA 87,628-632]. Here we show that the KIS-1 translocation breakpoint is located 1807 base pairs upstream of exon 1A of PAX-5, thus bringing the potent Emu enhancer of the IgH gene into close proximity of the PAX-5 promoters. These data suggest that deregulation of PAX-5 gene transcription by the t(9;14)(pl3;q32) translocation contributes to the pathogenesis of small lymphocytic lymphomas with plasmacytoid differentiation.
