Knowledge about the world phylogeny of human mitochondrial DNA (mtDNA) is essential not only for evaluating the pathogenic role of specific mtDNA mutations but also for performing reliable association studies between mtDNA haplogroups and complex disorders. In the past few years, the main features of the East Asian portion of the mtDNA phylogeny have been determined on the basis of complete sequencing efforts, but representatives of several basal lineages were still lacking. Moreover, some recently published complete mtDNA sequences did apparently not fit into the known phylogenetic tree and conflicted with the established nomenclature. To refine the East Asian mtDNA tree and resolve data conflicts, we first completely sequenced 20 carefully selected mtDNAs--likely representatives of novel sub-haplogroups--and then, in order to distinguish diagnostic mutations of novel haplogroups from private variants, we applied a 'motif-search' procedure to a large sample collection. The novel information was incorporated into an updated East Asian mtDNA tree encompassing more than 1000 (near-) complete mtDNA sequences. A reassessment of the mtDNA data from a series of disease studies testified to the usefulness of such a refined mtDNA tree in evaluating the pathogenicity of mtDNA mutations. In particular, the claimed pathogenic role of mutations G3316A, T3394C, A4833G and G15497A appears to be most questionable as those initial claims were derived from anecdotal findings rather than e.g. appropriate association studies. Following a guideline based on the phylogenetic knowledge as proposed here could help avoiding similar problems in the future.

The Northwestern Pacific has a unique tectonic and geographical history with several marginal seas separating Asia from the Pacific Ocean. During low sea level periods of Pleistocene glaciations, populations might have been isolated in three marginal seas: the Sea of Japan, East China Sea and South China Sea. Following postglacial sea level rise, we would expect the populations isolated in the three regions to have been homogenized by high dispersal potential. To assess these hypotheses, we explore the intraspecific phylogeographical patterns in redlip mullet, Chelon haematocheilus. Fragments of 435 bp at the 5' end of mitochondrial DNA control region were sequenced for 272 individuals from nine localities over most of the species' range. Three distinct lineages were detected, which might have diverged in the three marginal seas during Pleistocene low sea levels. Contrary to homogenization expectation, there were strong differences in the geographical distribution of the three lineages. Analyses of molecular variance and the population statistic Phi(ST) also revealed significant genetic structure among populations of the three marginal seas. These results indicate that gene flow in Chelon haematocheilus is far more restricted spatially than predicted by the potential dispersal capabilities of this species. The lack of phylogeographical structure in East China Sea may reflect a recent range expansion after the last glacial maximum and insufficient time to attain migration-drift equilibrium.

Constitutive ablation of the Yin Yang 1 (YY1) transcription factor in mice results in peri-implantation lethality. In this study, we used homologous recombination to generate knockout mice carrying yy1 alleles expressing various amounts of YY1. Phenotypic analysis of yy1 mutant embryos expressing ϳ75%, ϳ50%, and ϳ25% of the normal complement of YY1 identified a dosage-dependent requirement for YY1 during late embryogenesis. Indeed, reduction of YY1 levels impairs embryonic growth and viability in a dose-dependent manner. Analysis of the corresponding mouse embryonic fibroblast cells also revealed a tight correlation between YY1 dosage and cell proliferation, with a complete ablation of YY1 inducing cytokinesis failure and cell cycle arrest. Consistently, RNA interference-mediated inhibition of YY1 in HeLa cells prevents cytokinesis, causes proliferative arrest, and increases cellular sensitivity to various apoptotic agents. Genome-wide expression profiling identified a plethora of YY1 target genes that have been implicated in cell growth, proliferation, cytokinesis, apoptosis, development, and differentiation, suggesting that YY1 coordinates multiple essential biological processes through a complex transcriptional network. These data not only shed new light on the molecular basis for YY1 developmental roles and cellular functions, but also provide insight into the general mechanisms controlling eukaryotic cell proliferation, apoptosis, and differentiation.Regulation of fundamental cellular processes such as homeostasis, growth, proliferation, apoptosis, and differentiation involves complex networks of transcription factors as well as chromatin-remodeling proteins. Dysregulation of a wide variety of transcriptional regulators has been linked to various developmental defects and diseases, such as tumorigenesis.Yin Yang 1 (YY1; also called delta, NF-E1, and UCRBP) is a ubiquitously expressed GLI-Krüppel zinc finger-containing transcription factor (23,28,44,60). It is highly conserved from Xenopus to humans and has been shown to be the vertebrate homolog of the Drosophila melanogaster polycomb group protein Pleiohomeotic (2, 16, 64). YY1 is a multifunctional protein which can act as a transcriptional repressor or activator through combinatorial interactions with various other transcription factors, coactivators, and corepressors as well as chromatin-remodeling complexes displaying opposite functions, including the histone acetyltransferase p300/CBP, the arginine methyltransferase PRMT1, and the histone deacetylases HDAC1 and HDAC2 (4,[9][10][11][12]26,34,35,45,47,57,62,65,80,82,83).Since its original isolation, YY1 has been shown to control an ever-growing number of viral and cellular genes, among which are the human immunodeficiency virus type 1 and human papillomavirus oncogenes E6 and E7, several proto-oncogenes (c-myc, c-fos, and errb2), cdc-6 (cell division cycle 6 homolog), the DNA replication-dependent histone H3.2 gene, as well as various others (53,59,68,76). With a few exceptions, many YY1 target genes hav...