|Genome-wide mapping of histone H4 serine-1 phosphorylation during sporulation in Saccharomyces cerevisiae.|
Govin, J; Schug, J; Krishnamoorthy, T; Dorsey, J; Khochbin, S; Berger, SL
Nucleic acids research
We previously showed that histone H4 serine-1 phosphorylation (H4S1ph) is evolutionarily conserved during gametogenesis, and contributes to post-meiotic nuclear compaction and to full completion of sporulation in the yeast Saccharomyces cerevisiae. Previous studies showed that H4S1ph and another modification of the same histone, H4 acetylation (H4ac), do not occur together and have opposing roles during DNA double-strand break (DSB) repair. In this study, we investigated the relationship between these marks during yeast sporulation. H4S1ph and H4ac co-exist globally during later stages of sporulation, in contrast to DSB repair. Genome-wide mapping during sporulation reveals accumulation of both marks over promoters of genes. Prevention of H4S1ph deposition delays the decline in transcription that normally occurs during spore maturation. Taken together, our results indicate that H4S1ph deposition reinforces reduced transcription that coincides with full spore compaction, without disrupting the local acetylation signature. These studies indicate distinctive features of a histone H4 modification marking system during sporulation compared with DSB repair.Full Text Article
|X-ray crystallographic studies on fibrinogen and fibrin.|
Doolittle, R F
J. Thromb. Haemost., 1: 1559-65 (2003)
More than a dozen crystal structures of fibrinogen and fibrin fragments have been reported, including a structure of a native fibrinogen. The majority of the other structures are fragments D and d-dimer crystallized in the presence or absence of synthetic peptide ligands patterned on the A and B 'knobs'. Overall, fibrinogens or their fragments from four different species--human, bovine, chicken and lamprey--have been studied so far, with only minor differences in the structures being observed. Although these studies have thrown much light on the details of the fibrinogen to fibrin conversion, much remains to be found out.
|Hereditary disorders of fibrinogen.|
Matsuda, M and Sugo, T
Ann. N. Y. Acad. Sci., 936: 65-88 (2001)
Fibrinogen, a 340-kDa plasma protein, is composed of two identical molecular halves each consisting of three non-identical A alpha-, B beta- and gamma-chain subunits held together by multiple disulfide bonds. Fibrinogen is shown to have a trinodular structure; that is, one central nodule, the E domain, and two identical outer nodules, the D-domains, linked by two coiled-coil regions. After activation with thrombin, a pair of binding sites comprising Gly-Pro-Arg is exposed in the central nodule and combines with its complementary binding site a in the outer nodule of another molecules. By using crystallographic analysis, the alpha-amino group of alpha Gly-1 is shown to be juxtaposed between gamma Asp-364 and gamma Asp-330, and guanidino group of alpha Arg-3 between the carboxyl group of gamma Asp-364 and gamma Gln-329 in the a site. Half molecule-staggered, double-stranded protofibrils are thus formed. Upon abutment of two adjacent D domains on the same strand, D-D self association takes place involving Arg-275, Tyr-280, and Ser-300 of the gamma-chain on the surface of the abutting two D domains. Thereafter, carboxyl-terminal regions of the alpha-chains are untethered and interact with those of other protofibrils leading to the formation of thick fibrin bundles and networks. Although many enigmas still remain concerning the exact mechanisms of these molecular interactions, fibrin assembly proceeds in a highly ordered fashion. In this review, these molecular interactions of fibrinogen and fibrin are discussed on the basis of the data provided by hereditary dysfibrinogens on introducing representative molecules at each step of fibrin clot formation.