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Cell Identity (cell + identity)
Selected AbstractsEpigenetic dysregulation in cognitive disordersEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2009Johannes Gräff Abstract Epigenetic mechanisms are not only essential for biological functions requiring stable molecular changes such as the establishment of cell identity and tissue formation, they also constitute dynamic intracellular processes for translating environmental stimuli into modifications in gene expression. Over the past decade it has become increasingly clear that both aspects of epigenetic mechanisms play a pivotal role in complex brain functions. Evidence from patients with neurodegenerative and neurodevelopmental disorders such as Alzheimer's disease and Rett syndrome indicated that epigenetic mechanisms and chromatin remodeling need to be tightly controlled for proper cognitive functions, and their dysregulation can have devastating consequences. However, because they are dynamic, epigenetic mechanisms are also potentially reversible and may provide powerful means for pharmacological intervention. This review outlines major cognitive disorders known to be associated with epigenetic dysregulation, and discusses the potential of ,epigenetic medicine' as a promising cure. [source] Alteration of enhancer of polycomb 1 at 10p11.2 is one of the genetic events leading to development of adult T-cell leukemia/lymphomaGENES, CHROMOSOMES AND CANCER, Issue 9 2009Shingo Nakahata Adult T-cell leukemia/lymphoma (ATLL) is a malignant tumor caused by latent human T-lymphotropic virus 1 (HTLV-1) infection. We previously identified a common breakpoint cluster region at 10p11.2 in acute-type ATLL by spectral karyotyping. Single nucleotide polymorphism array comparative genomic hybridization analysis of the breakpoint region in three ATLL-related cell lines and four patient samples revealed that the chromosomal breakpoints are localized within the enhancer of polycomb 1 (EPC1) gene locus in an ATLL-derived cell line (SO4) and in one patient with acute-type ATLL. EPC1 is a human homologue of the E(Pc) enhancer of polycomb gene of Drosophila. Inappropriate expression of the polycomb group gene family has been linked to the loss of normal gene silencing pathways, which can contribute to the loss of cell identity and malignant transformation in many kinds of cancers. In the case of the SO4 cell line, which carried a der(10)t(2;10)(p23;p11.2) translocation, EPC1 was fused with the additional sex combs-like 2 (ASXL2) gene at 2p23.3 (EPC1/ASXL2). In the case with an acute-type ATLL, who carried a der(10)del(10)(p11.2)del(10)(q22q24) translocation, a putative truncated EPC1 gene (EPC1tr) was identified. Overexpression of EPC1/ASXL2 enhanced cell growth in T-leukemia cells, and a GAL4-EPC1/ASXL2 fusion protein showed high transcriptional activity. Although a GAL4-EPC1tr fusion protein did not activate transcription, overexpression of EPC1tr accelerated cell growth in leukemia cells, suggesting that the EPC1 structural abnormalities in the SO4 cell line and in the patient with acute-type ATLL may contribute to leukemogenesis. © 2009 Wiley-Liss, Inc. [source] AtDEK1 is essential for specification of embryonic epidermal cell fateTHE PLANT JOURNAL, Issue 1 2005Kim L. Johnson Summary The specification of epidermal (L1) identity occurs early during plant embryogenesis. Here we show that, in Arabidopsis, AtDEK1 encodes a key component of the embryonic L1 cell-layer specification pathway. Loss of AtDEK1 function leads to early embryo lethality characterized by a severe loss of cell organization in the embryo proper and abnormal cell divisions within the suspensor. Markers for L1 identity, ACR4 and ATML1, are not expressed in homozygous mutant embryos. In order to clarify the function of AtDEK1 further, an RNAi knockdown approach was used. This allowed embryos to partially complete embryogenesis before losing AtDEK1 activity. Resulting seedlings showed a specific loss of epidermal cell identity within large portions of the cotyledons. In addition, meristem structure and function was systematically either reduced or entirely lost. AtDEK1 expression is not restricted to the L1 epidermal cell layer at any stage in development. This is consistent with AtDEK1 playing an upstream role in the continuous generation or interpretation of positional information required for epidermal specification. Our results not only identify a specific role for AtDEK1 during embryogenesis, but underline the potential key importance of L1 specification at the globular stage for subsequent progression through embryogenesis. [source] Fungal sex genes,searching for the ancestorsBIOESSAYS, Issue 8 2008Lorna A. Casselton The sex-determining genes of fungi reside at one or two specialised regions of the chromosome known as the mating type (MAT) loci. The genes are sufficient to determine haploid cell identity, enable compatible mating partners to attract each other, and prepare cells for sexual reproduction after fertilisation. How conserved are these genes in different fungal groups? New work1 seeks an answer to this question by identifying the sex-determining regions of an early diverged fungus. These regions bear remarkable similarity to those described in other fungi, but the sex proteins they encode belong to only a single class of transcription factor, the high mobility group (HMG), indicating that these are likely to be ancestral to other proteins recruited for fungal sex. BioEssays 30:711,714, 2008. © 2008 Wiley Periodicals, Inc. [source] Losing B cell identityBIOESSAYS, Issue 3 2008Sebastian Carotta The transcription factor Pax5 is essential for the initial commitment of hematopoietic progenitors to the B cell lineage. Recently, our understanding of the lineage commitment process has been extended with the finding that Pax5 is also continuously required throughout B cell development to reinforce commitment, as inactivation of Pax5 in mature B cells results in their de-differentiation to a progenitor stage that is capable of multi-lineage potential.1 The reliance of B cell identity on a single gene is not without its problems as the loss of Pax5 results in B cell malignancies in mouse models and mutation in human PAX5 is the most-common genetic lesion in acute lymphoblastic leukemia. BioEssays 30:203,207, 2008. © 2008 Wiley Periodicals, Inc. [source] | ||||||||||