Genomic organization of the 3'-region of the human MUC5AC mucin gene: additional evidence for a common ancestral gene for the 11p15.5 mucin gene family.
Ontology highlight
ABSTRACT:
SUBMITTER: Buisine MP
PROVIDER: S-EPMC1219534 | biostudies-other | 1998 Jun
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Human mucin gene MUC5AC is clustered with MUC2, MUC5B and MUC6 on chromosome 11p15.5. We report here the full length cDNA sequence upstream of the repetitive region of human MUC5AC. We have also determined the sequence of its large central tandem repeat array. The 5'-region reveals high degree of sequence similarity with MUC2 and MUC5B and codes for 1336 amino acids organized into a signal peptide, four pro-von Willebrand factor-like D domains (D1, D2, D' and D3) and a short domain which connects to the central repetitive region. In the central region, 17 major domains have been identified. Nine code for cysteine-rich domains (Cys-domains 1-9) and exhibit high sequence similarity to the cysteine-rich domains described in the central region of MUC2 and MUC5B. Cys-domains 1-5 are interspersed by domains enriched with serine, threonine, and proline residues. Cys-domains 1-9 are interspersed by four domains (TR1-TR4) composed of various numbers of MUC5AC-type repeats. Southern-blot analyses reveal allelic variations both in length and nucleotide sequence. The length polymorphism which is due to variable numbers of tandem repeats is located in TR1 and TR4, whereas a mutation polymorphism detected with TaqI is located in Cys-domain 6. In this study, the organization of MUC5AC has been entirely elucidated showing extensive similarity to the other chromosome 11p15 MUC genes, particularly MUC5B, and providing additional arguments for common evolution from a single ancestral gene.
| S-EPMC1222110 | biostudies-other
Project description:The genomic organizations and functions of many miRNA genes have been described in recent years, but the origin and evolution of miRNAs in the exons of protein-coding genes are not well understood. The overlap of miR-650 genes with the protein-coding region of immunoglobulin lambda variable (IGVL) region genes has given a unique opportunity to witness a birth of miRNA gene. Both sequence comparisons and structure predictions indicate that the miR-650 genes are present in multiple copies and overlap in the same transcription orientation with the leader exon of primate IGVL genes of a specific phylogenetic clan (clan II). By reconstructing the phylogeny of the clan II IGVL genes, the stages in which the mutations accumulated in the leader exon and gave rise to a stable hairpin structure of miR-650 could be documented. The copy number variation of miR-650 genes among different species is the result of the duplication or deletion of the IGVL genes. To my knowledge, this is the first report of a genomic association between miRNA and the protein-coding genes of a multigene family. Analysis of the upstream region of the leader exon suggests that the IGVL and the mir-650 genes use the same promoter region for their transcription. However, in contrast to the general expectation about the expression of miRNAs that overlap with other genes in the same transcriptional orientation, this analysis provides evidence that the miR-650 gene is apparently transcribed independently of the IGVL gene with which it overlaps because they are expressed in different cell types.
| S-EPMC2727374 | biostudies-literature
Project description:Some mucin genes have been detected during human embryonic and fetal organ development; however, little is known about mucin expression in epidermal development, neither in humans nor in other species. The present research was developed to explore Muc5ac skin expression during prenatal and postnatal rat development. Immunohistochemistry (IHC), Western blotting (WB) and RT-PCR were employed. By IHC, Muc5ac protein was found early in embryonic epidermis from day 13 of gestation until seven days after birth when the surface epidermis became negative and the reaction was restricted to secreting sebum cells. In coincidence with IHC findings, WB analysis showed a band at approximately 200KDa at the same periods of development. Results were also confirmed by RT-PCR. Muc5ac expression in rat embryonic epidermis suggests that Muc5ac may play a protective role in embryonic skin previous to birth which may be replaced by pile covering. To our knowledge, this is the first report which confirmed Muc5ac expression during skin development. Muc5ac expression in rat embryonic epidermis suggests that Muc5ac may play a protective role in embryonic skin previous to birth which may be replaced by pile covering. To our knowledge, this is the first report which confirmed Muc5ac expression during skin development.
| S-EPMC4378216 | biostudies-literature
Project description:A novel large multigene family was recently identified in the human pathogen Trypanosoma cruzi, causative agent of Chagas disease, and corresponds to approximately 6% of the parasite diploid genome. The predicted gene products, mucin-associated surface proteins (MASPs), are characterized by highly conserved N- and C-terminal domains and a strikingly variable and repetitive central region. We report here an analysis of the genomic organization and expression profile of masp genes. Masps are not randomly distributed throughout the genome but instead are clustered with genes encoding mucin and other surface protein families. Masp transcripts vary in size, are preferentially expressed during the trypomastigote stage and contain highly conserved 5' and 3' untranslated regions. A sequence analysis of a trypomastigote cDNA library reveals the expression of multiple masp variants with a bias towards a particular masp subgroup. Immunofluorescence assays using antibodies generated against a MASP peptide reveals that the expression of particular MASPs at the cell membrane is limited to subsets of the parasite population. Western blots of phosphatidylinositol-specific phospholipase C (PI-PLC)-treated parasites suggest that MASP may be GPI-anchored and shed into the medium culture, thus contributing to the large repertoire of parasite polypeptides that are exposed to the host immune system.
| S-EPMC2691823 | biostudies-literature
Project description:In asthma, airflow obstruction is thought to result primarily from inflammation-triggered airway smooth muscle (ASM) contraction. However, anti-inflammatory and smooth muscle-relaxing treatments are often temporary or ineffective. Overproduction of the mucin MUC5AC is an additional disease feature that, while strongly associated pathologically, is poorly understood functionally. Here we show that Muc5ac is a central effector of allergic inflammation that is required for airway hyperreactivity (AHR) to methacholine (MCh). In mice bred on two well-characterized strain backgrounds (C57BL/6 and BALB/c) and exposed to two separate allergic stimuli (ovalbumin and Aspergillus extract), genetic removal of Muc5ac abolishes AHR. Residual MCh responses are identical to unchallenged controls, and although inflammation remains intact, heterogeneous mucous occlusion decreases by 74%. Thus, whereas inflammatory effects on ASM alone are insufficient for AHR, Muc5ac-mediated plugging is an essential mechanism. Inhibiting MUC5AC may be effective for treating asthma and other lung diseases where it is also overproduced.
| S-EPMC4333679 | biostudies-literature
Project description:To understand the mucociliary clearance system, mucins were visualized by light, confocal and electron microscopy, and mucus was stained by Alcian blue and tracked by video microscopy on tracheal explants of newborn piglets. We observed long linear mucus bundles that appeared at the submucosal gland openings and were transported cephalically. The mucus bundles were shown by mass spectrometry and immunostaining to have a core made of MUC5B mucin and were coated with MUC5AC mucin produced by surface goblet cells. The transport speed of the bundles was slower than the airway surface liquid flow. We suggest that the goblet cell MUC5AC mucin anchors the mucus bundles and thus controls their transport. Normal clearance of the respiratory tree of pigs and humans, both rich in submucosal glands, is performed by thick and long mucus bundles.
| S-EPMC5596833 | biostudies-literature
Project description:MUC5AC is a well-known gastric differentiation marker, which has been frequently used for the classification of stomach cancer. However, the molecular mechanism of regulation of MUC5AC expression remains to be elucidated. In previous studies, we have shown that Gli regulated MUC5AC transcription through the Gli-binding motif in the 5' region of MUC5AC. Gli played important roles, but independently was not sufficient for MUC5AC expression. In this study, we analyzed a 4010 bp fragment of the 5'-flanking promoter region of the human MUC5AC gene by luciferase assay, and found a novel distal enhancer region located between -1434 bp to -3000 bp upstream from the first ATG initiation codon. This region is composed of repetitive DNA sequences 5'-TCACTCAC-3'. The strength of enhancer activities depended on the length of the repetitive region. The tandem repeats are conserved among primates, but not in other mammals. The tandem repeat regions enhanced promoter activities not only of MUC5AC but also of other genes. The enhancer effect of the tandem repeat regions was maintained even when inverted. ChIP analysis revealed that H3K9me3 binds to the tandem repeat regions. Together, our results suggest that the tandem repeat region in the MUC5AC promoter has the potential to act as a strong enhancer, and H3K9me3 may contribute to histone modifications of this region.
| S-EPMC6449733 | biostudies-literature
Project description:Acute lung injury (ALI) is associated with high morbidity and mortality in critically ill patients. At present, the functional contribution of airway mucins to ALI is unknown. We hypothesized that excessive mucus production could be detrimental during lung injury. Initial transcriptional profiling of airway mucins revealed a selective and robust induction of MUC5AC upon cyclic mechanical stretch exposure of pulmonary epithelia (Calu-3). Additional studies confirmed time- and stretch-dose-dependent induction of MUC5AC transcript or protein during cyclic mechanical stretch exposure in vitro or during ventilator-induced lung injury in vivo. Patients suffering from ALI showed a 58-fold increase in MUC5AC protein in their bronchoalveolar lavage. Studies of the MUC5AC promoter implicated nuclear factor ?B in Muc5ac induction during ALI. Moreover, mice with gene-targeted deletion of Muc5ac?/? experience attenuated lung inflammation and pulmonary edema during injurious ventilation. We observed that neutrophil trafficking into the lungs of Muc5ac?/? mice was selectively attenuated. This implicates that endogenous Muc5ac production enhances pulmonary neutrophil trafficking during lung injury. Together, these studies reveal a detrimental role for endogenous Muc5ac production during ALI and suggest pharmacological strategies to dampen mucin production in the treatment of lung injury.
| S-EPMC3890100 | biostudies-literature
Project description:With its airborne transmission and prolonged latency period, Mycobacterium tuberculosis spreads worldwide as one of the most successful bacterial pathogens and continues to kill millions of people every year. M. tuberculosis lineage 1 is inferred to originate ancestrally based on the presence of the 52-bp TbD1 sequence and analysis of single nucleotide polymorphisms. Previously, we briefly reported the complete genome sequencing of M. tuberculosis strains 96121 and 96075, which belong to the ancient Manila family and modern Beijing family respectively. Here we present the comprehensive genomic analyses of the Manila family in lineage 1 compared to complete genomes in lineages 2-4. Principal component analysis of the presence and absence of CRISPR spacers suggests that Manila isolate 96121 is distinctly distant from lineages 2-4. We further identify a truncated whiB5 gene and a putative operon consisting of genes encoding a putative serine/threonine kinase PknH and a putative ABC transporter, which are only found in the genomes of Manila family isolates. Six single nucleotide polymorphisms are uniquely conserved in 38 Manila strains. Moreover, when compared to M. tuberculosis H37Rv, 59 proteins are under positive selection in Manila family isolate 96121 but not in Beijing family isolate 96075. The unique features further serve as biomarkers for Manila strains and may shed light on the limited transmission of this ancestral lineage outside of its Filipino host population.
| S-EPMC5386241 | biostudies-literature
Project description:In a previous study we isolated a partial cDNA with a tandem repeat of 48 bp, which allowed us to map a novel human mucin gene named MUC4 to chromosome 3q29. Here we report the organization and sequence of the 5'-region and its junction with the tandem repeat array of MUC4. Analysis of three overlapping genomic clones allowed us to obtain a partial restriction map of MUC4 and to locate the complete 48 bp tandem repeat domain on a PstI/EcoRI genomic fragment that exhibits a very large variation in number of tandem repeats (7-19 kb). cDNA clonal extension allowed us to obtain the entire 5' coding region of MUC4. Exon 1 consists of a 5' untranslated region and an 82 bp fragment encoding the signal peptide. This latter shows a high degree of similarity to the signal peptide of another apomucin, ASGP-1. Exon 2 is extremely large and contains a unique sequence that is followed by the whole tandem repeat domain. It encodes only one cysteine residue, making MUC4 different from mucin genes belonging to the 11p15.5 family. Moreover, an intron downstream from the tandem repeat array consists mainly of a 15 bp tandem repeat that exhibits a polymorphism in having a variable number of tandem repeats.
| S-EPMC1219535 | biostudies-other