Clusters of Master Control Genes Regulate the Development of Higher Organisms

Lewis, E. B.

doi:10.1001/jama.1992.03480110100042

Cited by 106 publications

(28 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Subsequently, indications that regulatory sequence competition might be a more general biological regulatory phenomenon began to emerge. The Drosophila HOM-C complex genes (as well as possibly their vertebrate counterparts) were proposed to be regulated in a competitive manner (Lewis 1992), and a conceptually similar scheme to chicken [3/e-globin gene competitive interactions has been invoked to explain the developmental behavior of the alternatively imprinted Igf2 and H19 genes (Sasaki et al 1992;Bartolomei et al 1993). Clearly any control network where complex regulatory patterns must be elicited from multiple cis elements must now be considered as possible focal points for the involvement of competitive transcriptional interactions.…”

Section: Competitive Gene Regulationmentioning

confidence: 99%

Synergistic regulation of human beta-globin gene switching by locus control region elements HS3 and HS4.

Bungert¹,

Davé²,

Lim³

et al. 1995

Genes Dev.

186

236

View full text Add to dashboard Cite

Proper tissue-and developmental stage-specific transcriptional control over the five genes of the human ~-globin locus is elicited in part by the locus control region (LCR), but the molecular mechanisms that dictate this determined pattern of gene expression during human development are still controversial. By use of homologous recombination in yeast to generate mutations in the LCR within a yeast artificial chromosome (YAC) bearing the entire human 13-globin gene locus, followed by injection of each of the mutated YACs into murine ova, we addressed the function of LCR hypersensitive site (HS) elements 3 and 4 in human 13-globin gene switching. The experiments revealed a number of unexpected properties that are directly attributable to LCR function. First, deletion of either HS3 or HS4 core elements from an otherwise intact YAC results in catastrophic disruption of globin gene expression at all erythroid developmental stages, despite the presence of all other HS elements in the YAC transgenes. If HS3 is used to replace HS4, gene expression is normal at all developmental stages. Conversely, insertion of the HS4 element in place of HS3 results in significant expression changes at every developmental stage, indicating that individual LCR HS elements play distinct roles in stage-specific [~-type globin gene activation. Although the HS4 duplication leads to alteration in the levels of ¢-and ~/-globin mRNAs during embryonic erythropoiesis, total [3-type globin mRNA synthesis is balanced, thereby leading to the conclusion that all of the human [3-locus genes are competitively regulated. In summary, the human [3-globin HS elements appear to form a single, synergistic functional entity called the LCR, and HS3 and HS4 appear to be individually indispensable to the integrity of this macromolecular complex.

show abstract

Section: Competitive Gene Regulationmentioning

confidence: 99%

Synergistic regulation of human beta-globin gene switching by locus control region elements HS3 and HS4.

Bungert¹,

Davé²,

Lim³

et al. 1995

Genes Dev.

186

236

View full text Add to dashboard Cite

show abstract

“…(2) These genes are conserved throughout the animal kingdom and act as master control genes that govern regional patterning along the anteroposterior axis of the organism (reviewed in Ref. 3). The Abd-B gene (4) was shown genetically to control proper development of the 5-9th abdominal segments.…”

Section: Introductionmentioning

confidence: 99%

Chromatin looping mediates boundary element promoter interactions

Celniker¹,

Drewell²

2006

BioEssays

View full text Add to dashboard Cite

One facet of the control of gene expression is long-range promoter regulation by distant enhancers. It is an important component of the regulation of genes that control metazoan development and has been appreciated for some time but the molecular mechanisms underlying this regulation have remained poorly understood. A recent study by Cleard and colleagues1 reports the first in vivo evidence of chromatin looping and boundary element promoter interaction. Specifically, they studied the function of a boundary element within the cis-regulatory region of the Abdominal-B (Abd-B) gene of Drosophila melanogaster.

show abstract

“…1B ). The hom eotic category was defined by Drosophila m utations that produc ed norm al structures at abnorm al positions (Lewis, 1992), a criterion that applies to heterotaxies with a norm al spleen or bilobed lung on the right. The comparison of hum an situs determination to the process for insect segm ent identity assum es that com mon steps are involved in conve rting identical units into symm etric, then asym m etric structures (W eyl, 195 2); bo un daries (m idline º segm ent bo rders) are first established to demarcate sym metric em bryoni c regions , followed by oriented differentiation of those regions to establish asymm etry (situs º segm ental differences).…”

Section: R E S U Lt S : a M O D El F O R Hu M A N S It U S Fo R M A Tmentioning

confidence: 99%

A Model for Human Situs Determination

Wilson¹

1996

Laterality

View full text Add to dashboard Cite

Alterations of human laterality range from situs reversal or consensus isometry to isolated anomalies of the cardiac, respiratory, gastrointestinal, skeletal, and central nervous systems. A mechanism for human situs determination has been derived from the general model of , with steps involving A-P axis, D-V axis, midline, global situs, and local situs specification. Comparison with Drosophila segmentation is supported by maternal transmission of certain human situs defects and mutation of appropriate Drosophila gene homologues in the human W aardenburg and Greig syndromes. Anteroposterior gradients in expression of vertebrate homeotic genes may relate to a proposed hierarchy of regional laterality decisions. Early alterations in A-P or D-V axis polarity would produce situs reversal in 100% of individuals, as observed in pure situs inversus, homozygous inv mice or manipulated Xenopus embryos. Later alterations would permit random right±left decisions and account for heterotaxy in 50% of affected individuals, as observed in poly/asplenia or homozygous iv mice. Randomisation of brain asymmetry could explain why situs but not brain laterality may be reversed in humans, with forebrain situs reversal or isometry leading to brain anomalies. Homologues of Drosophila genes regulating axis polarity, heart and gut development are attractive candidates in human laterality disorders, but none is uniquely localised to the 6q14±q21 or 9q32±q34, 7q22, 10q21±22, 11q13 or 11q25, 12q13, 13qter, or Xq24±q27.1 chromosome regions highlighted by heterotaxic patients or mutant mice. IN TR O D U C T IO NSuperimposed on the bilateral symmetry of vertebrates are a coordina ted group of right±left differences that comprise individual laterality or situs. This article presents a model for hum an situs determ ination that is based on the sequential process defined for insect segmentation (Fig. 1). Diverse anom alies of hum an laterality (Fig. 2) can be related to particular steps in this model, with implications for delineating the responsible genetic mutations.Model for human situs determination (A) with comparison to fruit fly segmentation (B). Boxes at the right represent undifferentiated early embryosÐ i.e. the bilaminar disc stageÐ prior to anteroposterio (A-P) and dorsoventral (D-V) axis formation. Classes of segmentation genes are indicated with human homologues in parentheses (see text). M olecules m1±m5 represent products of Drosophila homeotic genes, while``F' ' represents the asymmetric molecule postulated by .

show abstract

Clusters of Master Control Genes Regulate the Development of Higher Organisms

Cited by 106 publications

References 78 publications

Synergistic regulation of human beta-globin gene switching by locus control region elements HS3 and HS4.

Synergistic regulation of human beta-globin gene switching by locus control region elements HS3 and HS4.

Chromatin looping mediates boundary element promoter interactions

A Model for Human Situs Determination

Contact Info

Product

Resources

About