1,721,016 research outputs found
Polymorphisms and DNA methylation: two ways for functional differences in the 3' regulatory region of the IgH locus
Full text linkThe IgH locus in mouse and human has a 3' regulatory region (3'RR)
with multiple DNaseI hypersensitive sites. In the human, but not in the
mouse, the sites (HS3, HS1.2 and HS4) are duplicated. One unit is
downstream of the Cα-1 gene and a second unit is downstream of the Cα-2
gene. Human HS1,2 enhancers show polymorphic features.
In the mouse, HS3A, HS1.2, HS3B and HS4 are enhancers involved in
the expression and class switching of immunoglobulin heavy chain genes.
A recently identified downstream region, which contains hypersensitive
sites HS5, HS6 and HS7, has been hypothesized to serve as an insulator of
the Igh locus. This downstream region is associated with marks of active
chromatin throughout B cell development and contains binding sites for
CTCF, a protein associated with mammalian insulators. CTCF binding to
many of its cognate DNA sites is prevented by DNA methylation. Previous
studies using genomic Southern analysis have shown changes in DNA
methylation in the upstream region of the murine 3' RR during B cell
development.
In the first part of this work I identified the polymorphic structure of
human HS1,2, and its distribution in some populations and in some
immunological diseases. The data suggest that the HS1,2 enhancer that lies
downstream of the Cα-1 gene has four alleles, one of which, allele *2, is
more frequent in some immunological disorders and less frequent in the
sub-Saharan region. I have also observed using EMSA that protein binding
is different in the four alleles.
Furthermore I have studied changes in DNA methylation in the murine
3'RR during B cell development by digesting genomic DNA with
methylation-sensitive restriction enzymes, such as HpaII and MaeII,
followed by PCR. The data revealed that the 3’RR is methylated in
embryonic stem cells. ES cells derived from histone H1 depleted mice
showed a reduction in methylation as compared to their respective wildtype
counterparts. I have detected a progressive loss of DNA methylation
during B cell development. DNase I HS sites HS4, HS5 and HS7 are the
earliest regulated and unmethylated sites in cell lines reflecting early stages
of B development, while the HS1.2 and HS3B enhancers are unmethylated
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only in plasma cell lines. DNA methylation is also reduced in spleni
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Genomic comparison of the sequenze contributing to the 3D structure of the IgH3’ regulatory region (≥30kb) in vertebrates: conservation of a large palindromic structure with a polymorphism on the internal enhancer
No full textHaplotypes associated with alleles of the immunoglobulin heavy chain enhancer HS1,2 of the 3¢ regulatory region in patients with psor- iatic arthritis
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The functional VNTR of IGH enhancer HS1.2 associates with human longevity and interacts with TNFA promoter diplotype in a population of Central Italy
No full textThe dysregulation of both immune and inflammatory responses occurring with aging is believed to substantially contribute to morbidity and mortality in humans. We have already reported the association of the functional Variable Number of Tandem Repeat (VNTR) at the Immunoglobulin heavy chain (. IGH) enhancer HS1.2 with Immunoglobulin levels and with several autoimmune diseases. Herein we tested the association of the VNTR at the HS1.2 enhancer with human longevity, also evaluating the possible modulatory effect of TNFA promoter diplotype (rs361525/rs1800629). HS1.2 enhancer genotypes have been determined for 193 unrelated healthy individuals from Central Italy divided into two groups: Group 1 (18-84. yrs, mean age 56.8. ±. 19.4) and Group 2 (85-100. yrs, mean age 93.0. ±. 3.5). Homozygous subjects for *2 allele were significantly disadvantaged in reaching higher life-expectancy (OR. =. 0.457, p. =. 0.021). A significant interaction between TNFA promoter diplotype status, HS1.2 2/2 genotype and the two Groups was found (p. =. 0.014). Of note, TNFA -. 308A allele seems to exert a protective effect in HS1.2 2/2 carriers. These results support the hypothesis of an important role of HS1.2 VNTR in the puzzle of the immune-system regulation, evidenced also by the potential interaction with TNFA. Moreover, the previous results showing the association of HS1.2 *2 allele with inflammatory phenomena are consistent with the hypothesis that this allele is a detrimental factor in reaching advanced age
Evolution of human IgH3'EC duplicated structures: both enhancers HS1,2 are polymorphic with variation of transcription factor's consensus sites
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