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Alice Tay

Publications and source records attributed to Alice Tay.

8 recordsLinked to original sources
PubMed2006

Ancient noncoding elements conserved in the human genome.

Cartilaginous fishes represent the living group of jawed vertebrates that diverged from the common ancestor of human and teleost fish lineages about 530 million years ago. We generated approximately 1.4x genome sequence coverage for a cartilaginous fish, the elephant shark (Callorhinchus milii), and compared this genome with the human genome to identify conserved noncoding elements (CNEs). The elephant shark sequence revealed twice as many CNEs as were identified by whole-genome comparisons between teleost fishes and human. The ancient vertebrate-specific CNEs in the elephant shark and human genomes are likely to play key regulatory roles in vertebrate gene expression.

Animals↗
PubMed2006

Highly conserved syntenic blocks at the vertebrate Hox loci and conserved regulatory elements within and outside Hox gene clusters.

Hox genes in vertebrates are clustered, and the organization of the clusters has been highly conserved during evolution. The conservation of Hox clusters has been attributed to enhancers located within and outside the Hox clusters that are essential for the coordinated "temporal" and "spatial" expression patterns of Hox genes in developing embryos. To identify evolutionarily conserved regulatory elements within and outside the Hox clusters, we obtained contiguous sequences for the conserved syntenic blocks from the seven Hox loci in fugu and carried out a systematic search for conserved noncoding sequences (CNS) in the human, mouse, and fugu Hox loci. Our analysis has uncovered unusually large conserved syntenic blocks at the HoxA and HoxD loci. The conserved syntenic blocks at the human and mouse HoxA and HoxD loci span 5.4 Mb and 4 Mb and contain 21 and 19 genes, respectively. The corresponding regions in fugu are 16- and 12-fold smaller. A large number of CNS was identified within the Hox clusters and outside the Hox clusters spread over large regions. The CNS include previously characterized enhancers and overlap with the 5' global control regions of HoxA and HoxD clusters. Most of the CNS are likely to be control regions involved in the regulation of Hox and other genes in these loci. We propose that the regulatory elements spread across large regions on either side of Hox clusters are a major evolutionary constraint that has maintained the exceptionally long syntenic blocks at the HoxA and HoxD loci.

Animals↗
PubMed2005

STAT4 is a target of the hematopoietic zinc-finger transcription factor Ikaros in T cells.

STAT4 is a transcription factor activated in response to IL-12, and is involved in Th1 cell development. The molecular mechanisms controlling the transcription of the STAT4 gene are however, unclear. Sequence comparison of the 5' flanking regions of human, mouse and pufferfish (Fugu rubripes) Stat4 genes revealed a high frequency of Ikaros (Ik) binding elements in all three species. We then investigated the role of Ik binding elements in the human STAT4 promoter using Jurkat T cells. Transactivation, electrophoretic mobility shift assay and RNA interference-mediated gene knockdown experiments revealed that Ik is involved in the regulation of STAT4 in human T cells.

Animals↗
PubMed2003

Molecular cloning of the pufferfish (Takifugu rubripes) Mx gene and functional characterization of its promoter.

Mx proteins are members of a family of interferon-inducible genes that are expressed by cells in response to viral infection. They are important determinants of innate immunity against viral infection in vertebrates. We cloned the pufferfish ( Takifugu rubripes) Mx gene and sequenced 80 kb from the Mx locus. The Fugu Mx gene spans 3.4 kb from the transcription start site to the polyadenylation signal, and is made up of 12 exons and 11 introns. The protein sequence encoded by the Fugu Mx gene is 77%, 48%, and 51% identical to that of trout Mx1, chicken Mx, and mouse Mx1 genes, respectively. The Fugu Mx gene is expressed in a variety of tissues, with high expression detected in the heart, gill, kidney, intestine, and brain. Analysis of the 5'-flanking sequence of the gene showed the presence of two interferon-stimulated response elements (ISRE) at positions -51 to 38 and -97 to 85, relative to the transcription start site. The Fugu Mx promoter was inducible by human IFN-beta in the human hepatoma (Huh7) cells and by polyinosinic: polycytidilic acid in the top minnow hepatoma (PLHC-1) cells. Deletion analysis of the promoter showed that both ISREs contributed to inducibility. These results demonstrate that the molecular mechanisms involved in Mx gene regulation are conserved between fish and mammals.

Amino Acid Sequence↗
PubMed2002

Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes.

The compact genome of Fugu rubripes has been sequenced to over 95% coverage, and more than 80% of the assembly is in multigene-sized scaffolds. In this 365-megabase vertebrate genome, repetitive DNA accounts for less than one-sixth of the sequence, and gene loci occupy about one-third of the genome. As with the human genome, gene loci are not evenly distributed, but are clustered into sparse and dense regions. Some "giant" genes were observed that had average coding sequence sizes but were spread over genomic lengths significantly larger than those of their human orthologs. Although three-quarters of predicted human proteins have a strong match to Fugu, approximately a quarter of the human proteins had highly diverged from or had no pufferfish homologs, highlighting the extent of protein evolution in the 450 million years since teleosts and mammals diverged. Conserved linkages between Fugu and human genes indicate the preservation of chromosomal segments from the common vertebrate ancestor, but with considerable scrambling of gene order.

Animals↗
PubMed2002

Conserved regulation of the lymphocyte-specific expression of lck in the Fugu and mammals.

The lck gene encodes a lymphocyte-specific protein-tyrosine kinase that is implicated in T cell maturation and signaling. In mammals, the transcription of the lck gene is regulated by two independent promoters, the proximal promoter, which is active in thymocytes, and the distal promoter, which dominates in mature T cells. In the human and mouse lck gene loci, the two promoter elements are separated by at least 40 kb and 10 kb, respectively. In this study, we have cloned and sequenced 60 kb from the pufferfish (Fugu rubripes) lck locus. The promoter region of the Fugu lck spans only 4.2 kb and contains a proximal and a distal promoter in the 2.3-kb region adjacent to the coding sequence. By generating transgenic mice, we have demonstrated that the compact promoter of the Fugu lck contains regulatory elements that direct expression to lymphoid organs of mice. We were able to localize the regulatory elements to a short region of 830 bp without losing specificity to cultured human T cell line. These results show that the basic mechanisms that mediate lymphocyte-specific expression are conserved between teleosts and mammals. The short promoter of the Fugu lck isolated by us offers a powerful tool for labeling T cells, targeting expression, and manipulating T cell activity in fishes as well as in mammals.

Amino Acid Sequence↗
PubMed2002

Novel vertebrate genes and putative regulatory elements identified at kidney disease and NR2E1/fierce loci.

Fierce (frc) mice are deleted for nuclear receptor 2e1 (Nr2e1), and exhibit cerebral hypoplasia, blindness, and extreme aggression. To characterize the Nr2e1 locus, which may also contain the mouse kidney disease (kd) allele, we compared sequence from human, mouse, and the puffer fish Fugu rubripes. We identified a novel gene, c222389, containing conserved elements in noncoding regions. We also discovered a novel vertebrate gene conserved across its length in prokaryotes and invertebrates. Based on a dramatic upregulation in lactating breast, we named this gene lactation elevated-1 (LACE1). Two separate 100-bp elements within the first NR2E1 intron were virtually identical between the three species, despite an estimated 450 million years of divergent evolution. These elements represent strong candidates for functional NR2E1 regulatory elements in vertebrates. A high degree of conservation across NR2E1 combined with a lack of interspersed repeats suggests that an array of regulatory elements embedded within the gene is required for proper gene expression.

Alternative Splicing↗