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21.
Sequences flanking hypersensitive sites of the beta-globin locus control region are required for synergistic enhancement
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Molete JM Petrykowska H Bouhassira EE Feng YQ Miller W Hardison RC 《Molecular and cellular biology》2001,21(9):2969-2980
The major distal regulatory sequence for the beta-globin gene locus, the locus control region (LCR), is composed of multiple hypersensitive sites (HSs). Different models for LCR function postulate that the HSs act either independently or synergistically. To test these possibilities, we have constructed a series of expression cassettes in which the gene encoding the enhanced green fluorescent protein (EGFP) is under the control of DNA fragments containing single and multiple HSs of the LCR. LCR DNA fragments containing only the minimal region needed for position-independent expression (HS cores) or containing cores plus flanking sequences (HS units) were compared to ascertain whether conserved sequences between the HS cores contributed to enhancement. Expression of these constructs was measured after targeted integration into three defined loci in murine erythroleukemia cells using recombinase-mediated cassette exchange. At all three marked loci, synergistic enhancement of expression was observed in cassettes containing a combination of HS2, HS3, and HS4 units. In contrast, HS2, HS3, and HS4 cores (without flanking sequences) give an activity equivalent to the sum of the activities of the individual HS cores. These data suggest a model in which an HS core plus flanking regions, bound by specific proteins, forms a structure needed for interaction with other HS units to confer strong enhancement by the LCR. The three targeted integration sites differ substantially in their permissivity for expression, but even the largest LCR construct tested could not overcome these position effects to confer equal expression at all three sites. 相似文献
22.
Phylogenetic tests of the hypothesis of block duplication of homologous genes on human chromosomes 6, 9, and 1 总被引:8,自引:1,他引:7
There are 10 gene families that have members on both human chromosome 6
(6p21.3, the location of the human major histocompatibility complex [MHC])
and human chromosome 9 (mostly 9q33-34). Six of these families also have
members on mouse chromosome 17 (the mouse MHC chromosome) and mouse
chromosome 2. In addition, four of these families have members on human
chromosome 1 (1q21-25 and 1p13), and two of these have members on mouse
chromosome 1. One hypothesis to explain these patterns is that members of
the 10 gene families of human chromosomes 6 and 9 were duplicated
simultaneously as a result of polyploidization or duplication of a
chromosome segment ("block duplication"). A subsequent block duplication
has been proposed to account for the presence of representatives of four of
these families on human chromosome 1. Phylogenetic analyses of the 9 gene
families for which data were available decisively rejected the hypothesis
of block duplication as an overall explanation of these patterns. Three to
five of the genes on human chromosomes 6 and 9 probably duplicated
simultaneously early in vertebrate history, prior to the divergence of
jawed and jawless vertebrates, and shortly after that, all four of the
genes on chromosomes 1 and 9 probably duplicated as a block. However, the
other genes duplicated at different times scattered over at least 1.6
billion years. Since the occurrence of these clusters of related genes
cannot be explained by block duplication, one alternative explanation is
that they cluster together because of shared functional characteristics
relating to expression patterns.
相似文献
23.
Evolutionary distances for protein-coding sequences: modeling site- specific residue frequencies 总被引:13,自引:8,他引:5
Estimation of evolutionary distances from coding sequences must take into
account protein-level selection to avoid relative underestimation of longer
evolutionary distances. Current modeling of selection via site-to-site rate
heterogeneity generally neglects another aspect of selection, namely
position-specific amino acid frequencies. These frequencies determine the
maximum dissimilarity expected for highly diverged but functionally and
structurally conserved sequences, and hence are crucial for estimating long
distances. We introduce a codon- level model of coding sequence evolution
in which position-specific amino acid frequencies are free parameters. In
our implementation, these are estimated from an alignment using methods
described previously. We use simulations to demonstrate the importance and
feasibility of modeling such behavior; our model produces linear distance
estimates over a wide range of distances, while several alternative models
underestimate long distances relative to short distances. Site-to-site
differences in rates, as well as synonymous/nonsynonymous and
first/second/third-codon-position differences, arise as a natural
consequence of the site-to-site differences in amino acid frequencies.
相似文献
24.
High-level expression of the Endo-beta-N-acetylglucosaminidase F2 gene in E.coli: one step purification to homogeneity 总被引:1,自引:0,他引:1
The Endo F2gene was overexpressed in E.coli as a fusion protein joined to
the maltose-binding protein. MBP-Endo F2was found in a highly enriched
state as insoluble, inactive inclusion bodies. Extraction of the inclusion
bodies with 20% acetic acid followed by exhaustive dialysis rendered the
fusion protein active and soluble. MBP-Endo F2was digested with Factor
Xaand purified on Q-Sepharose. The enzyme was homogeneous by SDS-PAGE, and
appeared as a single symmetrical peak on HPLC. Analysis of the
amino-terminus demonstrated conclusively that recombinant Endo F2was
homogeneous and identical to the native enzyme.
相似文献
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BUALUANG FAIYUE MOHAMMED J. AL‐AZZAWI TIMOTHY J. FLOWERS 《Plant, cell & environment》2010,33(5):702-716
Although an apoplastic pathway (the so‐called bypass flow) is implicated in the uptake of Na+ by rice growing in saline conditions, the point of entry of this flow into roots remains to be elucidated. We investigated the role of lateral roots in bypass flow using the tracer trisodium‐8‐hydroxy‐1,3,6‐pyrenetrisulphonic acid (PTS) and the rice cv. IR36. PTS was identified in the vascular tissue of lateral roots using both epifluorescence microscopy and confocal laser scanning microscopy. Cryo‐scanning electron microscopy and epifluorescence microscopy of sections stained with berberine‐aniline blue revealed that the exodermis is absent in the lateral roots. We conclude that PTS can move freely through the cortical layers of lateral roots, enter the stele and be transported to the shoot via the transpiration stream. 相似文献
28.
29.
CXC chemokine ligand 10 controls viral infection in the central nervous system: evidence for a role in innate immune response through recruitment and activation of natural killer cells
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Trifilo MJ Montalto-Morrison C Stiles LN Hurst KR Hardison JL Manning JE Masters PS Lane TE 《Journal of virology》2004,78(2):585-594
How chemokines shape the immune response to viral infection of the central nervous system (CNS) has largely been considered within the context of recruitment and activation of antigen-specific lymphocytes. However, chemokines are expressed early following viral infection, suggesting an important role in coordinating innate immune responses. Herein, we evaluated the contributions of CXC chemokine ligand 10 (CXCL10) in promoting innate defense mechanisms following coronavirus infection of the CNS. Intracerebral infection of RAG1(-/-) mice with a recombinant CXCL10-expressing murine coronavirus (mouse hepatitis virus) resulted in protection from disease and increased survival that correlated with a significant increase in recruitment and activation of natural killer (NK) cells within the CNS. Accumulation of NK cells resulted in a reduction in viral titers that was dependent on gamma interferon secretion. These results indicate that CXCL10 expression plays a pivotal role in defense following coronavirus infection of the CNS by enhancing innate immune responses. 相似文献
30.
In the last several years, interest has increased significantly about the endocannabinoids anandamide and 2-arachidonylglycerol, two lipid messengers that activate cannabinoid receptors. Quantification of these compounds in biological samples presents numerous technical challenges. Because of their low abundance, endocannabinoids are usually quantified by isotope dilution assays using mass spectrometry coupled to either gas chromatography or high-performance liquid chromatography. Although endocannabinoid levels in biological fluids, such as plasma and cerebrospinal fluid, can be directly determined by these techniques, the complex lipid profile of brain tissue samples mandates purification of lipid extracts before GC/MS analysis; this step is not necessary when using HPLC/MS. We have found that when silica gel chromatography is used for endocannabinoid purification, poor recovery and loss of deuterium from the internal standards lead to inaccurate estimation of endocannabinoid levels. By contrast, purification strategies using C(18) solid-phase extraction permits precise and reproducible GC/MS quantification of endocannabinoids in tissue samples. 相似文献