Immunoglobulins
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
Ig genes are transcribed at a low rate even before they rearrange. Very little or no protein is translated from these RNAs, and they are called sterile transcripts. After rearrangement, the immunoglobulin enhancers become active. An enhancer is a nucleotide sequence which can increase the rate of transcription of genes near it. In some way, V gene rearrangement alters the structure of the enhancer region, and immunoglobulin gene transcription increases greatly. The heavy chain immunoglobulin intronic enhancer is situated between the JH and CH gene clusters (Figure 4–6). A second enhancer in the region 3’ to the Cα gene has recently been identified in the heavy chain loci of rats and mice. Two ϰ enhancers exist, one in the intron separating Jϰ from Cϰ, and another 3’to Cϰ. Two enhancers in the λ locus have also been identified.
Operations on Genomic Intervals and Genome Arithmetic
Altuna Akalin in Computational Genomics with R, 2020
Download P300 ChIP-seq peaks data from the UCSC browser. The peaks are locations where P300 binds. The P300 binding marks enhancer regions in the genome. (HINT: group: “regulation”, track: “Txn Factor ChIP”, table:“wgEncodeRegTfbsClusteredV3”, you need to filter the rows for “EP300” name.) Check enrichment of H3K4me3, H3K27ac and DNase-seq (H1.ESC.dnase.chr20.bw) experiments on chr20 on and arounf the P300 binding-sites, use data from compGenomRData package. Make multi-heatmaps and metaplots. What is different from the TSS profiles? [Difficulty: Advanced]
The Scientific Basis of Medicine
John S. Axford, Chris A. O'Callaghan in Medicine for Finals and Beyond, 2023
Every protein is encoded by a DNA sequence within a gene at a defined locus on a chromosome. Codons of three sequential nucleotides encode a single amino acid or a stop signal. Regulatory regions containing target sites for various DNA-binding proteins flank the coding sequence and control gene expression. These regions form a vital part of the gene and their loss can have profound effects on protein expression. Mutations in control regions can cause disease, as evidenced by some of the haemoglobin gene mutations that cause thalassaemia. An upstream promoter provides binding sites for RNA polymerase and transcription factors. Functionally related enhancer sequences are located further afield and recruit various DNA-binding proteins that can regulate the efficiency of gene transcription. The transcriptional unit contains exons of coding DNA separated by introns, which play no part in the finished protein. A large portion of our genome is composed of repetitive DNA of unclear function.
A Woman with Missing Hb A2 Due to a Novel (εγ)δβ0-Thalassemia and a Novel δ-Globin Variant Hb A2-Gebenstorf (HBD: c.209G>A)
Published in Hemoglobin, 2020
Elisabeth Saller, Jeroen Knijnenburg, Cornelis L. Harteveld, Fabrizio Dutly
The human β-globin gene cluster consists of five genes arranged in chromosome 11 in the same order in which they are expressed during development: 5′-ε-, Gγ-, Aγ-, δ- and β-globin gene [Human Genome Variation Society (HGVS): 5′-HBE-HBG2-HBG1-HBD-HBB] [1]. Hb A2, which makes up for 2.5% of the total Hb in adults, is composed of two α- and two δ-globin chains (α2δ2) and can be detected only after birth, when the δ-globin gene expression is increasing and Hb A2 synthesis occurs. The ‘fetal to adult Hb switch’ takes place shortly before birth replacing Hb F (α2γ2) for Hb A (α2β2) as β chain production augments. This is controlled by enhancer-gene promoter interaction that results in recruitment of transcription factors that trigger gene expression. The β-locus control region (β-LCR) enhancer is located 50 kb upstream of the β-globin gene and consists of hypersensitive sites (HS) 1–5 [2]. A phenotypic β-thalassemia (β-thal) minor can be caused by mutation of the β gene, of a regulator such as BCL11A [3] or by deletion of the LCR enhancer itself.
Trophectoderm non-coding RNAs reflect the higher metabolic and more invasive properties of young maternal age blastocysts
Published in Systems Biology in Reproductive Medicine, 2023
Panagiotis Ntostis, Grace Swanson, Georgia Kokkali, David Iles, John Huntriss, Agni Pantou, Maria Tzetis, Konstantinos Pantos, Helen M. Picton, Stephen A. Krawetz, David Miller
Other functionalities involve the formation of a triple helix structure upstream of gene enhancers, that help recruit chromatin modifiers and promote enhancer RNA (eRNA) transcription (Postepska-Igielska et al. 2015; Blank-Giwojna et al. 2019). LncRNAs can regulate gene expression at the post-transcriptional, translational and post-translational level. They bear complementary regions that compete with microRNAs (miRNAs) targeting specific mRNAs, expression of which ultimately relies on their relative proportions (Bosson et al. 2014; Denzler et al. 2014; Grelet et al. 2017). They can also act as scaffolds supporting the generation of ribonucleoprotein complexes and as a guide that could bring these complexes to specific genome locations (Bouckenheimer et al. 2016). Finally, they can bind to proteins preventing interactions with their targets, providing in this regard a post-translational regulatory mechanism (Karreth et al. 2014).
Genetic investigation of ocular developmental genes in 52 patients with anophthalmia/microphthalmia
Published in Ophthalmic Genetics, 2018
Nair Gopinathan Vidya, Sankaranarayanan Rajkumar, Abhay R. Vasavada
Any variation that induces or inhibits the binding of transcription factors to the promoter/enhancer region of the gene can have an adverse effect on the gene function. The known polymorphism FOXE3 c.-14G>A variation was found to cause the loss of Oct-1, substitution of AP-1 for SP-1 and SP-1 for C/EBPalp. The SP-1, AP-1, and OCT-1 genes are ubiquitous transcription factors, while the expression of C/EBPalp is more restricted, but nevertheless apparent in a broad range of cell types. (63,68–72) They all are known to regulate gene expression by activating and/or repressing the transcription of genes. (63,68–70,72) Till now, it is not known how all these factors regulate the FOXE3 gene and how the loss or gain of these factors affects FOXE3 gene function in the lens. Therefore, future research involving knock-out studies is warranted to find the mechanism by which FOXE3 is regulated by these factors in the lens.
Related Knowledge Centers
- Activator
- DNA
- Immunoglobulin Heavy Chain
- Protein
- Genetics
- Base Pair
- Transcription
- Gene
- Transcription Factor
- Cis-Regulatory Element