scholarly journals Transcriptional Regulation and Implications for Controlling Hox Gene Expression

2022 ◽  
Vol 10 (1) ◽  
pp. 4
Author(s):  
Zainab Afzal ◽  
Robb Krumlauf
Keyword(s):  
Transcriptional Regulation ◽  
Molecular Mechanisms ◽  
Hox Genes ◽  
Regional Identity ◽  
Regulatory Mechanisms ◽  
Regulation Of Transcription ◽  
Axial Patterning ◽  
Hox Gene ◽  
Molecular Framework ◽  
Combinatorial Code

Hox genes play key roles in axial patterning and regulating the regional identity of cells and tissues in a wide variety of animals from invertebrates to vertebrates. Nested domains of Hox expression generate a combinatorial code that provides a molecular framework for specifying the properties of tissues along the A–P axis. Hence, it is important to understand the regulatory mechanisms that coordinately control the precise patterns of the transcription of clustered Hox genes required for their roles in development. New insights are emerging about the dynamics and molecular mechanisms governing transcriptional regulation, and there is interest in understanding how these may play a role in contributing to the regulation of the expression of the clustered Hox genes. In this review, we summarize some of the recent findings, ideas and emerging mechanisms underlying the regulation of transcription in general and consider how they may be relevant to understanding the transcriptional regulation of Hox genes.

Patterning the ascidian nervous system: structure, expression and transgenic analysis of the CiHox3 gene

Development ◽  
1999 ◽  
Vol 126 (21) ◽  
pp. 4737-4748 ◽  
Author(s):  
A. Locascio ◽  
F. Aniello ◽  
A. Amoroso ◽  
M. Manzanares ◽  
R. Krumlauf ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Hox Genes ◽  
Regional Identity ◽  
Regulatory Elements ◽  
System Structure ◽  
Anteroposterior Patterning ◽  
Hox Gene ◽  
The Central Nervous System ◽  
Group 3

Hox genes play a fundamental role in the establishment of chordate body plan, especially in the anteroposterior patterning of the nervous system. Particularly interesting are the anterior groups of Hox genes (Hox1-Hox4) since their expression is coupled to the control of regional identity in the anterior regions of the nervous system, where the highest structural diversity is observed. Ascidians, among chordates, are considered a good model to investigate evolution of Hox gene, organisation, regulation and function. We report here the cloning and the expression pattern of CiHox3, a Ciona intestinalis anterior Hox gene homologous to the paralogy group 3 genes. In situ hybridization at the larva stage revealed that CiHox3 expression was restricted to the visceral ganglion of the central nervous system. The presence of a sharp posterior boundary and the absence of transcript in mesodermal tissues are distinctive features of CiHox3 expression when compared to the paralogy group 3 in other chordates. We have investigated the regulatory elements underlying CiHox3 neural-specific expression and, using transgenic analysis, we were able to isolate an 80 bp enhancer responsible of CiHox3 activation in the central nervous system (CNS). A comparative study between mouse and Ciona Hox3 promoters demonstrated that divergent mechanisms are involved in the regulation of these genes in vertebrates and ascidians.

scholarly journals Identification, Characterization, and Regulatory Mechanisms of a Novel EGR1 Splicing Isoform

2019 ◽  
Vol 20 (7) ◽  
pp. 1548 ◽  
Author(s):  
Vincenza Aliperti ◽  
Giulia Sgueglia ◽  
Francesco Aniello ◽  
Emilia Vitale ◽  
Laura Fucci ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cell Types ◽  
Regulatory Mechanisms ◽  
Brain Diseases ◽  
Regulation Of Transcription ◽  
Biological Processes ◽  
Activation Domain ◽  
Post Translational Modifications ◽  
Pathological Conditions ◽  
Proliferation And Apoptosis

EGR1 is a transcription factor expressed in many cell types that regulates genes involved in different biological processes including growth, proliferation, and apoptosis. Dysregulation of EGR1 expression has been associated with many pathological conditions such as tumors and brain diseases. Known molecular mechanisms underlying the control of EGR1 function include regulation of transcription, mRNA and protein stability, and post-translational modifications. Here we describe the identification of a splicing isoform for the human EGR1 gene. The newly identified splicing transcript encodes a shorter protein compared to the canonical EGR1. This isoform lacks a region belonging to the N-terminal activation domain and although it is capable of entering the nucleus, it is unable to activate transcription fully relative to the canonical isoform.

Contribution of structural accessibility to the cooperative relationship of TF-lncRNA in myopia

2021 ◽  
Author(s):  
Hong Wang ◽  
Jing Li ◽  
Siyu Wang ◽  
Xiaoyan Lu ◽  
Guosi Zhang ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Molecular Mechanisms ◽  
Systematic Research ◽  
Regulation Of Transcription ◽  
Molecular Binding ◽  
Binding Force ◽  
Cooperative Relationship ◽  
Relationship Of ◽  
Spatial Architecture ◽  
Candidate Set

Abstract Transcriptional regulation is associated with complicated mechanisms including multiple molecular interactions and collaborative drive. Long noncoding RNAs (lncRNAs) have highly structured characteristics and play vital roles in the regulation of transcription in organisms. However, the specific contributions of conformation feature and underlying molecular mechanisms are still unclear. In the present paper, a hypothesis regarding molecular structure effect is presented, which proposes that lncRNAs fold into a complex spatial architecture and act as a skeleton to recruit transcription factors (TF) targeted binding, and which is involved in cooperative regulation. A candidate set of TF-lncRNA coregulation was constructed, and it was found that structural accessibility affected molecular binding force. In addition, transcription factor binding site (TFBS) regions of myopia-related lncRNA transcripts were disturbed, and it was discovered that base mutations affected the occurrence of significant molecular allosteric changes in important elements and variable splicing regions, mediating the onset and development of myopia. The results originated from structureomics and interactionomics and created conditions for systematic research on the mechanisms of structure-mediated TF-lncRNA coregulation in transcriptional regulation. Finally, these findings will help further the understanding of key regulatory roles of molecular allostery in cell physiological and pathological processes.

scholarly journals Mechanisms of Apoptosis-Related Long Non-coding RNAs in Ovarian Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Toshihiko Takeiwa ◽  
Kazuhiro Ikeda ◽  
Kuniko Horie-Inoue ◽  
Satoshi Inoue
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Therapy Resistance ◽  
Therapeutic Strategies ◽  
Regulatory Mechanisms ◽  
Ovarian Cancer Cells ◽  
Regulation Of Transcription ◽  
Advanced Stages ◽  
Non Coding Rnas

Ovarian cancer is a health-threatening malignancy of ovary in female reproductive systems and one of the most common gynecological malignancies worldwide. Due to rare early symptoms, ovarian cancers are often diagnosed at advanced stages and exhibit poor prognosis. Thus, efforts have been paid to develop alternative diagnostic and therapeutic strategies for the disease. Recent studies have presented that some long non-coding RNAs (lncRNAs) play roles in apoptosis of ovarian cancer cells through various mechanisms involved in the regulation of transcription factors, histone modification complexes, miRNAs, and protein stability. Because evasion of apoptosis in cancer cells facilitates to promote tumor progression and therapy resistance, apoptosis regulatory mechanisms of lncRNAs may be promising new targets in ovarian cancer. In this review, we introduce the recent findings in regard to the molecular mechanisms of apoptosis-related lncRNAs in ovarian cancer cells.

scholarly journals Timed collinear activation of Hox genes during gastrulation controls the avian forelimb position

2018 ◽  
Author(s):  
Chloe Moreau ◽  
Paolo Caldarelli ◽  
Didier Rocancourt ◽  
Julian Roussel ◽  
Nicolas Denans ◽  
...  
Keyword(s):  
Natural Variation ◽  
Molecular Mechanisms ◽  
Hox Genes ◽  
Gene Activation ◽  
The Body ◽  
Three Dimensions ◽  
Limb Patterning ◽  
Hox Gene ◽  
Limb Position ◽  
Control Limb

SummaryLimb position along the body is highly consistent within one species but very variable among vertebrates. Despite major advances in our understanding of limb patterning in three dimensions, how limbs reproducibly form along the anteroposterior axis remains largely unknown. Hox genes have long been suspected to control limb position, however supporting evidences are mostly correlative and their role in this process remains unclear. Here we show that Hox genes determine the avian forelimb position in a two-step process: first, their sequential collinear activation during gastrulation controls the relative position of their own successive expression domains along the body axis. Then, within these collinear domains, Hox genes differentially activate or repress the genetic cascade responsible for forelimb initiation. Furthermore, we provide evidences that changes in the timing of collinear Hox gene activation might underlie natural variation in forelimb position between different birds. Altogether our results which characterize the cellular and molecular mechanisms underlying the regulation and natural variation of forelimb position in avians, show a direct and early role for Hox genes in this process.

Defined concentrations of a posteriorizing signal are critical for MafB/Kreisler segmental expression in the hindbrain

Development ◽  
1998 ◽  
Vol 125 (7) ◽  
pp. 1173-1181 ◽  
Author(s):  
A. Grapin-Botton ◽  
M.A. Bonnin ◽  
M. Sieweke ◽  
N.M. Le Douarin
Keyword(s):  
Gene Expression ◽  
Neural Crest ◽  
Leucine Zipper ◽  
Hox Genes ◽  
Paraxial Mesoderm ◽  
Regulatory Mechanisms ◽  
Expression Domain ◽  
Environmental Signals ◽  
Hox Gene ◽  
Segmental Expression

It has been shown by using the quail/chick chimera system that Hox gene expression in the hindbrain is influenced by positional signals arising from the environment. In order to decipher the pathway that leads to Hox gene induction, we have investigated whether a Hox gene regulator, the leucine zipper transcription factor MafB/Kr, is itself transcriptionally regulated by the environmental signals. This gene is normally expressed in rhombomeres (r) 5 and 6 and their associated neural crest. MafB/Kr expression is maintained in r5/6 when grafted into the environment of r3/4. On the contrary, the environment of rhombomeres 7/8 represses MafB/Kr expression. Thus, as previously shown for the expression of Hox genes, MafB/Kr expression is regulated by a posterior-dominant signal, which in this case induces the loss of expression of this gene. We also show that the posterior signal can be transferred to the r5/6 neuroepithelium by posterior somites (somites 7 to 10) grafted laterally to r5/6. At the r4 level, the same somites induce MafB/Kr in r4, leading it to behave like r5/6. The posterior environment regulates MafB/Kr expression in the neural crest as it does in the corresponding hindbrain level, showing that some positional regulatory mechanisms are shared by neural tube and neural crest cells. Retinoic acid beads mimic the effect produced by the somites in repressing MafB/Kr in r5/6 and progressively inducing it more rostrally as its concentration increases. We therefore propose that the MafB/Kr expression domain is defined by a molecule unevenly distributed in the paraxial mesoderm. This molecule would allow the expression of the MafB/Kr gene in a narrow window of concentration by activating its expression at a definite threshold and repressing it at higher levels, accounting for its limited domain of expression in only two rhombomeres. It thus appears that the regulation of MafB/Kr expression in the rhombomeres could be controlled by the same posteriorizing factor(s) as Hox genes.

scholarly journals Characterisation of the role and regulation of Ultrabithorax in sculpting fine-scale leg morphology

2020 ◽  
Author(s):  
Alexandra D. Buffry ◽  
Sebastian Kittelmann ◽  
Alistair P. McGregor
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Hox Genes ◽  
Regional Identity ◽  
Fine Scale ◽  
Hox Gene ◽  
Leg Development ◽  
Gene Regulatory ◽  
Leg Morphology

AbstractHox genes are expressed during embryogenesis and determine the regional identity of animal bodies along the antero-posterior axis. However, they also function post-embryonically to sculpt fine-scale morphology. To better understand how Hox genes are integrated into post-embryonic gene regulatory networks, we further analysed the role and regulation of Ultrabithorax (Ubx) during mesothoracic (T2) leg development in Drosophila melanogaster. Ubx represses leg trichomes in the proximal posterior region of the T2 femur (the so-called naked valley) and we found that it likely does so through activating the expression of microRNA-92a. We also identified a T2 leg enhancer of Ubx that recapitulates the temporal and regional activity of this Hox gene in these appendages. Analysis of motifs in this enhancer predicted that it is bound by Distal-less (Dll) and we found that knockdown of Dll results in the loss of trichomes on the T2 femur. This suggests that while Ubx activates microRNA-92a to repress trichomes in the naked valley region of the proximal femur, Dll may repress Ubx more distally to enable formation of trichomes. Taken together our results provide insights into how Ubx is integrated into a postembryonic gene regulatory network to determine fine-scale leg morphology.

scholarly journals Lin28a/let-7 pathway modulates the Hox code via Polycomb regulation during axial patterning in vertebrates

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Tempei Sato ◽  
Kensuke Kataoka ◽  
Yoshiaki Ito ◽  
Shigetoshi Yokoyama ◽  
Masafumi Inui ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Hox Genes ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
The Body ◽  
Tight Control ◽  
Tail Bud ◽  
Axial Patterning ◽  
Spatiotemporal Expression ◽  
Hox Code

The body plan along the anteroposterior axis and regional identities are specified by the spatiotemporal expression of Hox genes. Multistep controls are required for their unique expression patterns; however, the molecular mechanisms behind the tight control of Hox genes are not fully understood. In this study, we demonstrated that the Lin28a/let-7 pathway is critical for axial elongation. Lin28a–/– mice exhibited axial shortening with mild skeletal transformations of vertebrae, which were consistent with results in mice with tail bud-specific mutants of Lin28a. The accumulation of let-7 in Lin28a–/– mice resulted in the reduction of PRC1 occupancy at the Hox cluster loci by targeting Cbx2. Consistently, Lin28a loss in embryonic stem-like cells led to aberrant induction of posterior Hox genes, which was rescued by the knockdown of let-7. These results suggest that the Lin28/let-7 pathway is involved in the modulation of the ‘Hox code’ via Polycomb regulation during axial patterning.

Hox genes, clusters and collinearity

2018 ◽  
Vol 62 (11-12) ◽  
pp. 659-663 ◽  
Author(s):  
Robb Krumlauf
Keyword(s):  
Gene Family ◽  
Evolutionary Biology ◽  
Hox Genes ◽  
Gene Clusters ◽  
Regulatory Mechanisms ◽  
Homeotic Gene ◽  
Gene Complex ◽  
40Th Anniversary ◽  
Hox Gene ◽  
Conserved Gene

This year marks the 40th anniversary of the discovery by Ed Lewis of the property of collinearity in the bithorax gene complex in Drosophila. This landmark work illustrated the need to understand regulatory mechanisms that coordinate expression of homeotic gene clusters. Through the efforts of many groups, investigation of the Hox gene family has generated many fundamental findings on the roles and regulation of this conserved gene family in development, disease and evolution. This has led to a number of important conceptual advances in gene regulation and evolutionary biology. This article presents some of the history and advances made through studies on Hox gene clusters.

scholarly journals Hox gene duplications correlate with posterior heteronomy in scorpions

2014 ◽  
Vol 281 (1792) ◽  
pp. 20140661 ◽  
Author(s):  
Prashant P. Sharma ◽  
Evelyn E. Schwager ◽  
Cassandra G. Extavour ◽  
Ward C. Wheeler
Keyword(s):  
Whole Genome Duplication ◽  
Hox Genes ◽  
Genome Duplication ◽  
Regional Identity ◽  
Gene Duplications ◽  
Expression Domain ◽  
Hox Gene ◽  
Domain Boundaries ◽  
Centruroides Sculpturatus ◽  
Evolutionary Success

The evolutionary success of the largest animal phylum, Arthropoda, has been attributed to tagmatization, the coordinated evolution of adjacent metameres to form morphologically and functionally distinct segmental regions called tagmata. Specification of regional identity is regulated by the Hox genes, of which 10 are inferred to be present in the ancestor of arthropods. With six different posterior segmental identities divided into two tagmata, the bauplan of scorpions is the most heteronomous within Chelicerata. Expression domains of the anterior eight Hox genes are conserved in previously surveyed chelicerates, but it is unknown how Hox genes regionalize the three tagmata of scorpions. Here, we show that the scorpion Centruroides sculpturatus has two paralogues of all Hox genes except Hox3 , suggesting cluster and/or whole genome duplication in this arachnid order. Embryonic anterior expression domain boundaries of each of the last four pairs of Hox genes (two paralogues each of Antp , Ubx , abd-A and Abd-B ) are unique and distinguish segmental groups, such as pectines, book lungs and the characteristic tail, while maintaining spatial collinearity. These distinct expression domains suggest neofunctionalization of Hox gene paralogues subsequent to duplication. Our data reconcile previous understanding of Hox gene function across arthropods with the extreme heteronomy of scorpions.

Sign in / Sign up

Export Citation Format

Share Document