Characterization of a Widely Expressed Gene (LUC7-LIKE; LUC7L) Defining the Centromeric Boundary of the Human α-Globin Domain

Tufarelli, Cristina; Frischauf, Anna Maria; Hardison, Ross C.; Flint, Jonathan; Higgs, Douglas R.

doi:10.1006/geno.2000.6394

Cited by 29 publications

(26 citation statements)

References 29 publications

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“…In cows, pigs and hedgehogs, the only evolutionary lines in which the neighboring coding exon MCS-E2 is not conserved (Table 1), MCS-S2 has also undergone rapid sequence divergence, suggesting that conservation of MCS-S2 is required to act as a signal for the alternative splicing of MCS-E2. In support of this hypothesis, a phylogenetic footprint of MCS-S2 revealed two highly conserved (100% from human to chicken) sequences (AG-CATG), previously shown to be functional components of intronic control regions (ICRs), which regulate alternative splicing (33,34). Similar conserved ICRs were also found in MCS-S1, which lies close to another known alternatively spliced exon in the rhomboid-like gene (gene 5, Fig.…”

Section: Conservation Of Mcss In 22 Speciesmentioning

confidence: 59%

Annotation of cis-regulatory elements by identification, subclassification, and functional assessment of multispecies conserved sequences

Hughes

Cheng

Ventress

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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135

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An important step toward improving the annotation of the human genome is to identify cis-acting regulatory elements from primary DNA sequence. One approach is to compare sequences from multiple, divergent species. This approach distinguishes multispecies conserved sequences (MCS) in noncoding regions from more rapidly evolving neutral DNA. Here, we have analyzed a region of Ϸ238kb containing the human ␣ globin cluster that was sequenced and͞or annotated across the syntenic region in 22 species spanning 500 million years of evolution. Using a variety of bioinformatic approaches and correlating the results with many aspects of chromosome structure and function in this region, we were able to identify and evaluate the importance of 24 individual MCSs. This approach sensitively and accurately identified previously characterized regulatory elements but also discovered unidentified promoters, exons, splicing, and transcriptional regulatory elements. Together, these studies demonstrate an integrated approach by which to identify, subclassify, and predict the potential importance of MCSs.conserved noncoding elements ͉ gene regulation ͉ globin gene ͉ comparative genomics W ith the development of multiple computational algorithms and appropriate biological data, it is now possible to detect coding sequences relatively efficiently and accurately from primary DNA sequence (1). By contrast, it is still difficult to identify and assign function to noncoding sequences that include critical cisacting regulatory elements such as promoters, enhancers, silencers, locus control elements, nuclear matrix attachment sites, and origins of replication. A promising approach is to search for conserved orthologous noncoding sequences from multiple, evolutionarily diverse species (2-8), so-called multispecies conserved sequences (MCSs). However, at present, it is not established how best to design and carry out such searches. Furthermore, even when complete, it is not clear how to evaluate and prioritize MCSs for functional analysis.An important issue is to know which species to include in searches for MCSs. When comparing the sequences of distantly related species [e.g., birds and mammals, which diverged 310 million years (my) ago], cis elements may have diverged too much to be easily identified. By contrast, when comparing more closely related species (e.g., rodents and primates, which diverged 64-74 my ago), it may be difficult to distinguish between sequence homology resulting from a slow rate of evolution and the conservation of functionally important cis elements. Nevertheless, it is becoming clear that analyzing multiple species in different combinations adds significant power to the identification of functionally important cis-acting sequences (2, 3).Even when MCS can be unequivocally identified, there is often no way to judge how sensitive the searches have been. Do these routines overcall or undercall regulatory elements? Furthermore, the true functional significance of MCSs often remains untested and͞or unknown because there is u...

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Section: Conservation Of Mcss In 22 Speciesmentioning

confidence: 59%

Annotation of cis-regulatory elements by identification, subclassification, and functional assessment of multispecies conserved sequences

Hughes

Cheng

Ventress

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

135

130

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“…La question posée était donc le mode par lequel la délétion inactivait ce deuxième gène α. On n'a pu mettre en évidence ni la délétion d'un élément de régulation positive, ni en [4]. Il est transcrit dans la direction opposée à celle du locus α. Les auteurs ont alors formulé l'hypothèse selon laquelle le transcrit de ce gène, anormalement étendu du fait de la délétion, pouvait être responsable de la méthylation de la région promotrice de HBA2 et de l'extinction subséquente du gène.…”

Section: Nouvelleunclassified

Une nouvelle cause de maladie génétique: l’inactivation d’un gène par un transcrit d’ARN antisens

Labie

2004

Med Sci (Paris)

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Section: Introductionmentioning

confidence: 97%

“…Although a unique deletion in this locus has been reported in individuals with a-thalassemia, resulting in truncation of LUC7L as well as production of antisense RNA for the aglobin gene (Tufarelli et al, 2003), the physiological function of LUC7L per se remains obscure. In mammals, there is another gene closely related to the yeast gene LUC7 known as cisplatin resistance-associated over-expressed protein (CROP) or LUC7A (Nishii et al, 2000;Tufarelli et al, 2001). Different than yeast Luc7p, mammalian Luc7- (Fortes et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…In humans, the LUC7L gene, which lies on the centromeric side of the aglobin gene cluster on chromosome 16p13.3, is known to be transcribed in many types of tissues and cells (Tufarelli et al, 2001). A previous database search indicated that there are putative LUC7L paralogues in several species, including mice and D. melanogaster (Tufarelli et al, 2001). Although a unique deletion in this locus has been reported in individuals with a-thalassemia, resulting in truncation of LUC7L as well as production of antisense RNA for the aglobin gene (Tufarelli et al, 2003), the physiological function of LUC7L per se remains obscure.…”

Section: Introductionmentioning

confidence: 99%

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Serine–arginine-rich nuclear protein Luc7l regulates myogenesis in mice

Kimura

Hidaka

Kida

et al. 2004

Gene

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Characterization of a Widely Expressed Gene (LUC7-LIKE; LUC7L) Defining the Centromeric Boundary of the Human α-Globin Domain

Cited by 29 publications

References 29 publications

Annotation of cis-regulatory elements by identification, subclassification, and functional assessment of multispecies conserved sequences

Annotation of cis-regulatory elements by identification, subclassification, and functional assessment of multispecies conserved sequences

Une nouvelle cause de maladie génétique: l’inactivation d’un gène par un transcrit d’ARN antisens

Serine–arginine-rich nuclear protein Luc7l regulates myogenesis in mice

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