Disease relevance of TNP2

• Protein classes similar to TNP1 and TNP2 that are also found in human colonic adenocarcinomas are not detectable in polyps from familial polyposis-affected patients at times when no sign of malignancy has yet appeared [1].
• Both Lys-6 and Lys-65 were modified in TNP-2, and modification of Lys-65 caused a further reduction of the lethal toxicity to 12.6% [2].

High impact information on TNP2

• In addition, GRTH participated in the nuclear export of RNA messages (PGK2, tACE, and TP2) in a gene-specific manner [3].
• Thus, the MARs bounding the PRM1 --> PRM2 --> TNP2 protamine domain have many and varied functions [4].
• Methylation of G at the N-7 position with dimethyl sulfate did not affect the recognition of CpG island by TP2 [5].
• Preincubation of TP2 with 10 mM EDTA or 1 mM 1, 10-o-phenanthroline inhibited the complex formation by more than 90% [5].
• Rat spermatidal protein TP2 is a zinc metalloprotein with two atoms of zinc coordinated to cysteine and histidine residues and condenses alternating GC copolymer preferentially in a zinc dependent manner [Kundu, T. K., & Rao, M. R. S. (1995) Biochemistry 34,5143-5150] [5].

Biological context of TNP2

• The genes for three of these low molecular weight basic nuclear proteins exist as a single linear array of PRM1, PRM2, and TNP2 on human chromosome 16p13 [6].
• The members of the male haploid expressed protamine 1 (PRM1)-->protamine 2 (PRM2)-->transition protein 2 (TNP2) locus exist as a single, coordinately expressed genic domain [7].
• In mouse and human, the genes encoding protamines PRM1, PRM2 and transition protein TNP2 are found clustered together on chromosome 16 [8].
• To understand better the coordinate control governing this transformation, we have examined the localization and distribution of the human protamines PRM1 and PRM2 and transition protein TNP2 transcripts during human spermatogenesis [9].
• The expression of the PRM1, PRM2, and TNP2 genes facilitates the compaction and condensation of the genetic material within the developing spermatid [9].

Anatomical context of TNP2

• Analysis of the haploid-expressed human PRM1 --> PRM2 --> TNP2 genic domain has revealed two regions of attachment to the sperm nuclear matrix [10].
• CONCLUSION(S): In the present patient the breakpoint at 16p13.3 could have disrupted or harbored the PRM1, PRM2, or TNP2 genes responsible for the replacement of the histones involved in packaging the DNA into the sperm head [11].
• These data indicate that the human PRM1, PRM2, and TNP2 transcripts are expressed postmeiotically in round and elongating spermatids [9].
• Coordinate expression of the PRM1, PRM2, and TNP2 multigene locus in human testis [9].
• PRM1, PRM2, and TNP2 transcripts were abundant in association with round and elongating spermatids, located in the adluminal region of the seminiferous epithelium [9].

Associations of TNP2 with chemical compounds

• We demonstrate here that 525 bp of 5'- and 920 bp of 3'-flanking sequences of rat TNP2 gene could properly and efficiently direct chloramphenicol acetyltransferase gene expression to the postmeiotic male germ cells of transgenic mice [12].
• The condensation of the alternating copolymers by TP2 (incubated with 10 microM ZnSO4), namely, poly(dG-dC).poly(dG-dC) and poly(dA-dT).poly(dA-dT), was severalfold higher than condensation of either of the homoduplexes poly(dG).poly-(dC) and poly(dA).poly(dT) or rat oligonucleosomal DNA [13].
• The 5 kb transcript of tnp2 contains an open reading frame that shares 45% homology with part of the tnpD gene of En/Spm from maize and 48% homology with an open reading frame of the Tgm element from Glycine max [14].

Other interactions of TNP2

• Single-nucleotide polymorphisms and mutation analyses of the TNP1 and TNP2 genes of fertile and infertile human male populations [15].

Analytical, diagnostic and therapeutic context of TNP2

• In order to determine regulatory flanking sequences responsible for stage specific expression of TNP2 gene, different transgenic mice were generated by microinjection of fertilized eggs [12].
• We have now carried out a detailed analysis of the DNA condensing properties of TP2 with various polynucleotides using circular dichroism spectroscopy [13].
• In the present study, we have used a 40-mer oligonucleotide containing a human CpG island sequence to study its interaction with TP2 by gel mobility shift assays [5].
• Three major derivatives, TNP-1, TNP-2, and TNP-3, were separated by high-performance liquid chromatography (HPLC) from the reaction mixtures in the absence of Ca2+ [16].
• The results of amino acid analysis and sequence determination revealed that CDNP-PLA2 and TNP-1 contained one modified Lys residue at position 6, and both Lys-6 and Lys-62 were modified in TNP-2 [17].

References