ABSTRACT
As the obesity pandemic has accelerated, investigators have begun to explore alternative mechanisms linking circadian biology and sleep to adipose tissue metabolism and obesity. This manuscript reviews recent findings in murine and human models demonstrating the oscillatory expression of the mRNAs encoding the core circadian regulatory proteins in adipose tissue. Comparative transcriptomic analyses of circadian oscillating genes have been used to identify the 'delta sleep-inducing peptide immunoreactor', also known as 'glucocorticoid-induced leucine zipper (GILZ)', as a potential link in this chain. The GILZ gene has been found to differentially regulate stromal stem cell adipogenic and osteogenic differentiation in a reciprocal manner. In adipose and other metabolically active tissues, the circadian oscillation of GILZ expression is subject to entrainment by external stimuli. Together, these observations suggest that GILZ is an attractive candidate for future studies evaluating the role of circadian mechanisms in adipose tissue physiology and pathology.
Subject(s)
Adipogenesis/physiology , Adipose Tissue/metabolism , Circadian Rhythm/physiology , Delta Sleep-Inducing Peptide/metabolism , Leucine Zippers/physiology , Osteogenesis/physiology , Animals , Cell Differentiation/physiology , Delta Sleep-Inducing Peptide/genetics , Gene Expression Regulation , Glucocorticoids/pharmacology , Humans , Leucine Zippers/drug effects , Leucine Zippers/genetics , Mice , Obesity/etiology , Obesity/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcription FactorsABSTRACT
The human body displays central circadian rhythms of activity. Recent findings suggest that peripheral tissues, such as bone, possess their own circadian clocks. Studies have shown that osteocalcin protein levels oscillate over a 24-hour period, yet the specific skeletal sites involved and its transcriptional profile remain unknown. The current study aimed to test the hypothesis that peripheral circadian mechanisms regulate transcription driven by the osteocalcin promoter. Transgenic mice harboring the human osteocalcin promoter linked to a luciferase reporter gene were used. Mice of both genders and various ages were analyzed non-invasively at sequential times throughout 24-hour periods. Statistical analyses of luminescent signal intensity of osteogenic activity from multiple skeletal sites indicated a periodicity of ~ 24 hrs. The maxillomandibular complex displayed the most robust oscillatory pattern. These findings have implications for dental treatments in orthodontics and maxillofacial surgery, as well as for the mechanisms underlying bone remodeling in the maxillomandibular complex.
Subject(s)
Circadian Rhythm/genetics , Mandible/metabolism , Maxilla/metabolism , Osteocalcin/genetics , Animals , Carpal Bones/anatomy & histology , Carpal Bones/metabolism , Female , Gene Expression Regulation/genetics , Half-Life , Humans , Image Processing, Computer-Assisted/methods , Luciferases , Luminescence , Male , Mandible/anatomy & histology , Maxilla/anatomy & histology , Mice , Mice, Transgenic , Models, Animal , Osteogenesis/genetics , Promoter Regions, Genetic/genetics , Sex Factors , Skull/anatomy & histology , Skull/metabolism , Tail/anatomy & histology , Tail/metabolism , Tarsal Bones/anatomy & histology , Tarsal Bones/metabolism , Transcription, Genetic/geneticsABSTRACT
The expressed human genome is being sequenced and analyzed by disparate groups producing disparate data. The majority of the identified coding portion is in the form of expressed sequence tags (ESTs). The need to discover exonic representation and expression forms of full-length cDNAs for each human gene is frustrated by the partial and variable quality nature of this data delivery. A highly redundant human EST data set has been processed into integrated and unified expressed transcript indices that consist of hierarchically organized human transcript consensi reflecting gene expression forms and genetic polymorphism within an index class. The expression index and its intermediate outputs include cleaned transcript sequence, expression, and alignment information and a higher fidelity subset, SANIGENE. The STACK_PACK clustering system has been applied to dbEST release 121598 (GenBank version 110). Sixty-four percent of 1,313, 103 Homo sapiens ESTs are condensed into 143,885 tissue level multiple sequence clusters; linking through clone-ID annotations produces 68,701 total assemblies, such that 81% of the original input set is captured in a STACK multiple sequence or linked cluster. Indexing of alignments by substituent EST accession allows browsing of the data structure and its cross-links to UniGene. STACK metaclusters consolidate a greater number of ESTs by a factor of 1. 86 with respect to the corresponding UniGene build. Fidelity comparison with genome reference sequence AC004106 demonstrates consensus expression clusters that reflect significantly lower spurious repeat sequence content and capture alternate splicing within a whole body index cluster and three STACK v.2.3 tissue-level clusters. Statistics of a staggered release whole body index build of STACK v.2.0 are presented.
Subject(s)
Cluster Analysis , Consensus Sequence , Expressed Sequence Tags , Gene Expression , Algorithms , Databases, Factual , Genome, Human , Humans , Polymorphism, Single Nucleotide/genetics , Sequence AlignmentABSTRACT
We report an integrative technology for molecular biology studies in the field of transcription regulation by using Internet. A set of databases, programs, and systems are included into WWWMGS Web server. For example, the use of TRRD database information for site prediction is described. Using this method, the computer system SeqAnn was developed. The system performs the "real time" searching for prediction of initiation transcription site position according to database information. WWWMGS is available at URL: http://wwwmgs.bionet.nsc.ru/.
Subject(s)
Database Management Systems , Molecular Biology , Systems Integration , Base Sequence , Gene Expression Regulation , Internet , Transcription, GeneticABSTRACT
The primary structure of the cDNA copy of the evolutionary conserved gene Nc73EF from the region 73EF of Drosophila melanogaster was determined. Gene Nc73EF was shown to encode a protein highly homologous to the E1 subunit of human 2-oxoglutarate dehydrogenase, which catalyzes one of the key reactions of the Krebs cycle.
Subject(s)
Conserved Sequence , Drosophila melanogaster/genetics , Genes, Insect , Ketoglutarate Dehydrogenase Complex/genetics , Amino Acid Sequence , Animals , Base Sequence , Biological Evolution , Catalysis , Citric Acid Cycle , Genetic Code , Humans , Molecular Sequence Data , Sequence Homology, Amino Acid , Sequence Homology, Nucleic AcidABSTRACT
The repeated DNA sequence of wild ram (Ovis ammon) of 800 bp has been cloned. The blot-hybridization, in situ-hybridization, sequencing and computer analysis were used for the sequence analysis. It was shown that the cloned DNA is from 1.714 gm/cm3 repeated satellite DNA family. Fourteen highly homologous sequences were revealed in the nucleotide sequence databases. An analysis of their alignment revealed presence of two subfamilies (A and B). Average divergence of subfamily A. sequences (including the wild ram repeated sequence) from consensus is about 1%.
Subject(s)
DNA/genetics , DNA/isolation & purification , Repetitive Sequences, Nucleic Acid/genetics , Sheep/genetics , Animals , Animals, Wild , Base Sequence , Cells, Cultured , Consensus Sequence , DNA, Satellite/genetics , Goats/genetics , Male , Molecular Sequence Data , Sequence Alignment/methods , Sequence Analysis, DNA/methods , Sequence Homology, Nucleic AcidABSTRACT
The possibility of using oligonucleotides from MER1 family repeats as PCR primers for the amplification of human genome DNA fragments was studied. The recommended oligonucleotide primers were chosen by computer analysis of the data base of the EMBL (release 37.0) nucleotide sequences. Use of one of the oligonucleotides was shown to allow specific human DNA amplification to be carried out.
Subject(s)
DNA Fragmentation , Databases, Factual , Genome, Human , Multigene Family , Polymerase Chain Reaction/methods , Repetitive Sequences, Nucleic Acid , Base Sequence , DNA Primers , Gene Frequency , Humans , Molecular Sequence Data , Sequence Homology, Nucleic Acid , SoftwareABSTRACT
We report an object-oriented data handler and supplementary tools for the development of molecular genetics application software for various sequence analyses. Our data handler has a flexible and expandable format that supports the most common data types for molecular genetic software. New data types can be constructed in an object-oriented manner from the basic units. The data handler includes an object library, a format-converting program and a viewer that can visualize simultaneously the data contained in several files to construct a general picture from separate data. This software has been implemented on an IBM PC-compatible personal computer.
Subject(s)
Sequence Analysis, DNA/methods , Software , Atrial Natriuretic Factor/genetics , Base Sequence , DNA/genetics , Data Interpretation, Statistical , Databases, Factual , Evaluation Studies as Topic , Humans , Microcomputers , Molecular Biology , Molecular Sequence Data , Protein Precursors/genetics , Sequence Analysis, DNA/statistics & numerical dataABSTRACT
A new algorithm for data bank homology search is proposed. The principal advantages of the new algorithm are: (i) linear computation complexity; (ii) low memory requirements; and (iii) high sensitivity to the presence of local region homology. The algorithm first calculates indicative matrices of k-tuple 'realization' in the query sequence and then searches for an appropriate number of matching k-tuples within a narrow range in database sequences. It does not require k-tuple coordinates tabulation and in-memory placement for database sequences. The algorithm is implemented in a program for execution on PC-compatible computers and tested on PIR and GenBank databases with good results. A few modifications designed to improve the selectivity are also discussed. As an application example, the search for homology of the mouse homeotic protein HOX 3.1 is given.
