Biomedical subjects

Ya-Jun Li

Publications and source records attributed to Ya-Jun Li.

7 recordsLinked to original sources

PubMed2005

A conserved, extended chromatin opening within alpha-globin locus during development.

Histone modifications play an important role in eukaryotic gene regulation. However, the dynamic alteration of histone modification during development is poorly understood. In addition, the relationship between histone modification and globin gene switching remains unclear. Here, we assessed the dynamic pattern of histone modification (H3 acetylation, H4 acetylation, H3 K4 methylation, and H3 K79 methylation) along the murine alpha-globin locus, as well as along the human alpha-globin locus in transgenic mice, during globin gene switching in vivo. During the switching, histone modification at embryonic zeta-gene and fetal/adult alpha-genes displayed different developmental patterns. The level of histone modification at zeta-gene was developmentally regulated, in accordance with the level of zeta-gene expression, whereas the alpha-genes kept high level of histone modification at both developmental stages, regardless of their expression levels. Histone deacetylase inhibition selectively increased acetylation at the inactive zeta-gene in fetal livers, although it did not reactivate the gene expression. More importantly, an obvious increasing of histone modification level at major regulatory elements and fetal/adult alpha-genes was observed during the switching, suggesting that a conserved, extended chromatin opening within the locus occurs during globin gene switching.

Acetylation↗

PubMed2005

The influence of associative effects on the in vitro-estimated utilizable crude protein (uCP) of feeds for ruminants.

Nineteen feed mixtures, formulated with 16 single feeds, were used to study the influence of associative effects on utilizable crude protein (uCP) of feed mixtures. The in vitro incubation technique of Zhao and Lebzien (2000) was used for uCP determination. It was found that the in vitro-determined uCP (D-uCP) was significantly higher than the weighted uCP (W-uCP) of feed mixtures and there was a significant regressive relationship between W-uCP (x) [g x kg(-1)DM] and D-uCP (y) [g x kg(-1)DM]: y=(0.94 +/- 0.23)x + (18.78 +/- 35.58), r2=0.49, n=19, p < 0.01. It was concluded that there exist significant associative effects of feed mixtures on uCP. In formulation of rations for ruminants the D-uCP should be used instead of W-uCP. Because of the low regression coefficient of the equation above, the D-uCP cannot be estimated from the W-uCP.

Animal Feed↗

PubMed2004

Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates.

Hedgehog (Hh) signaling plays a major role in multiple aspects of embryonic development. A key issue in Hh signaling is to elucidate the molecular mechanism by which a Hh protein morphogen gradient is formed despite its membrane association. In this study, we used a combination of genetic, cellular, and biochemical approaches to address the role of lipid modifications in long-range vertebrate Hh signaling. Our molecular analysis of knockout mice deficient in Skn, the murine homolog of the Drosophila ski gene, which catalyzes Hh palmitoylation, and gene-targeted mice producing a nonpalmitoylated form of Shh indicates that Hh palmitoylation is essential for its activity as well as the generation of a protein gradient in the developing embryos. Furthermore, our biochemical data show that Hh lipid modifications are required for producing a soluble multimeric protein complex, which constitutes the major active component for Hh signaling. These results suggest that soluble Hh multimeric complex travels in the morphogenetic field to activate Hh signaling in distant Hh-responsive cells.

Animals↗

PubMed2004

Opening the chromatin for transcription.

Eukaryotic genomes are packaged into a dynamic hierarchy chromatin structure. In such a particular context, the transition from a repressed compacted chromatin to a rather extended fiber is necessary for transcription. The chromatin opening includes three events, the initial factor getting access to nucleosome DNA, local chromatin opening mediated by activator/coactivator, and transcription associated with extensive chromatin opening. Chromatin dynamics, which is DNA sequence dependent, and also occurs in condensed fiber, provides the opportunity for activators binding to DNA. Coactivators recruited by the activator open the chromatin locally. However, it appears that genes adopt distinct chromatin opening mechanisms according to whether the gene is induced expression, developmental and tissue-specific expression, or constitutive expression. In contrast to transcription initiation-related local chromatin opening, large scale of chromatin opening is associated with a functional enhancer as well as high transcription rate. How the transcription initiated from an enhancer or enhancer like modules, i.e. intergenic transcription, conducts the extensive chromatin opening is discussed. A model for long-range interaction that non-coding transcripts from enhancers may promote efficient communication with promoters is proposed.

Animals↗

PubMed2003

Martentoxin, a novel K+-channel-blocking peptide: purification, cDNA and genomic cloning, and electrophysiological and pharmacological characterization.

Martentoxin, a novel K+-channel-specific peptide has been purified and characterized from the venom of the East-Asian scorpion (Buthus martensi Karsch). The whole cDNA precursor sequence suggested that martentoxin was composed of 37 residues with a unique sequence compared with other scorpion neurotoxins. The genomic DNA of martentoxin showed an additional intron situated unexpectedly in the 5' UTR region, besides one located close to the C-terminal of the signal peptide. The patch-clamp recording found that martentoxin at the applied dose of 100 nm could strongly block large-conductance Ca2+-activated K+ (BKCa) currents in adrenal medulla chromaffin cells, and BKCa currents blocked by martentoxin could be fully recovered within 30 seconds after washing, which is at least 10 times faster than recovery after charybdotoxin. Meanwhile, a biosensor binding assay showed a fast association rate and a slow dissociation rate of martentoxin binding on rat brain synaptosomes. The binding of martentoxin on rat brain synaptosomes could be inhibited regularly by charybdotoxin, and gradually by toosendanin in a concentration-dependent manner, but not by either apamin or P03 from Buthus martensi. The results thus indicate that martentoxin is a new member in the family of K+-channel-blocking ligands.

Amino Acid Sequence↗

PubMed2002

Mouse dispatched mutants fail to distribute hedgehog proteins and are defective in hedgehog signaling.

Hedgehog (Hh) signaling plays a major role in multiple aspects of embryonic development, which involves both short- and long-range signaling from localized Hh sources. One unusual aspect of Hh signaling is the autoproteolytic processing of Hh followed by lipid modification. As a consequence, the N-terminal fragment of Hh becomes membrane anchored on the cell surface of Hh-producing cells. A key issue in Hh signaling is to understand the molecular mechanisms by which lipid-modified Hh protein is transported from its sites of synthesis and subsequently moves through the morphogenetic field. The dispatched gene, which encodes a putative multipass membrane protein, was initially identified in Drosophila and is required in Hh-producing cells, where it facilitates the transport of cholesterol-modified Hh. We report the identification of the mouse dispatched (Disp) gene and a phenotypic analysis of Disp mutant mice. Disp-null mice phenocopy mice deficient in the smoothened gene, an essential component for Hh reception, suggesting that Disp is essential for Hh signaling. This conclusion was further supported by a detailed molecular analysis of Disp knockout mice, which exhibit defects characteristic of loss of Hh signaling. We also provide evidence that Disp is not required for Hh protein synthesis or processing, but rather for the movement of Hh protein from its sites of synthesis in mice. Taken together, our results reveal a conserved mechanism of Hh protein movement in Hh-producing cells that is essential for proper Hh signaling.

Alleles↗

PubMed1999

Characteristics of BmK AS Binding to Rat Brain and Cockroach Nerve Cord Synaptosomes.

BmK AS, one novel neurotoxic polypeptide from Chinese scorpion Buthus martensi Karsch was labeled by (125)I with INDOGEN method. Iododerivative was used in binding experiments on mammal and insect synaptosomes. BmK AS binds specifically to a single class of non-interacting binding sites with high affinity (K(d)=1.49 nmol/L) and low capacity (B(max)=1.39 nmol/g) on rat brain synaptosomes. Likewise, BmK AS also binds specifically to a single class of non-interacting binding sites with high affinity (K(d)=0.79 nmol/L) and low capacity (B(max)=6.60 nmol/g) on cockroach nerve cord synaptosomes. It indicates that there are special target receptors for BmK AS type scorpion neurotoxins on both mammal and insect excitable cell membranes.

Journal Article↗