The remote transcriptional control of Hox genes

2018 ◽  
Vol 62 (11-12) ◽  
pp. 685-692 ◽  
Author(s):  
Claudia Gentile ◽  
Marie Kmita
Keyword(s):  
Long Range ◽  
Transcriptional Control ◽  
Hox Genes ◽  
Three Dimensional ◽  
Fruit Fly ◽  
Chromosome Conformation ◽  
Functional Relevance ◽  
Insulator Elements ◽  
Polycomb Repressive Complexes ◽  
Anterior Posterior

Since the discovery by Ed Lewis that the order of Hox genes on the chromosome reflects the partitioning of their patterning function along the anterior-posterior axis of the developing fruit fly embryo, extensive efforts have been dedicated to uncovering the regulatory events underlying the collinear expression of Hox genes. These studies have revealed various aspects of Hox regulation, including short-range and long-range transcriptional enhancers, insulator elements and non-coding RNAs. With the development of technologies allowing for high resolution probing of chromatin architecture, notably Chromosome Conformation Capture (3C)-based techniques, a clear relationship is emerging between long-range regulation of Hox genes and the three-dimensional organization of the genome. Here, we provide an overview of these studies and in particular we discuss the functional relevance of genome compartmentalization, CTCF- mediated insulation and the Polycomb Repressive Complexes in the remote control of Hox genes.

scholarly journals A re-inducible gap gene cascade patterns the anterior-posterior axis of insects in a threshold-free fashion

2018 ◽  
Author(s):  
Alena Boos ◽  
Jutta Distler ◽  
Heike Rudolf ◽  
Martin Klingler ◽  
Ezzat El-Sherif
Keyword(s):  
Gene Network ◽  
Hox Genes ◽  
Expression Patterns ◽  
Fruit Fly ◽  
Regulation Mechanism ◽  
Gap Gene ◽  
Speed Regulation ◽  
Gap Genes ◽  
Anterior Posterior ◽  
Anterior Posterior Axis

AbstractGap genes mediate the division of the anterior-posterior axis of insects into different fates through regulating downstream hox genes. Decades of tinkering the segmentation gene network of the long-germ fruit fly Drosophila melanogaster led to the conclusion that gap genes are regulated (at least initially) through a threshold-based French Flag model, guided by both anteriorly- and posteriorly-localized morphogen gradients. In this paper, we show that the expression patterns of gap genes in the intermediate-germ beetle Tribolium castaneum are mediated by a threshold-free ‘Speed Regulation’ mechanism, in which the speed of a genetic cascade of gap genes is regulated by a posterior gradient of the transcription factor Caudal. We show this by re-inducing the leading gap gene (namely, hunchback) resulting in the re-induction of the gap gene cascade at arbitrary points in time. This demonstrates that the gap gene network is self-regulatory and is primarily under the control of a posterior speed regulator in Tribolium and possibly all insects.

Dysregulation of HOX as a Potential Therapeutic Target in Breast Cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ji-Yeon Lee ◽  
Myoung Hee Kim
Keyword(s):  
Breast Cancer ◽  
Hox Genes ◽  
Therapeutic Potential ◽  
Expression Patterns ◽  
Genome Structure ◽  
Control Cell ◽  
Three Dimensional ◽  
Cellular Processes ◽  
Hox Protein

: HOX genes belong to the highly conserved homeobox superfamily, responsible for the regulation of various cellular processes that control cell homeostasis, from embryogenesis to carcinogenesis. The abnormal expression of HOX genes is observed in various cancers, including breast cancer; they act as oncogenes or as suppressors of cancer, according to context. In this review, we analyze HOX gene expression patterns in breast cancer and examine their relationship, based on the three-dimensional genome structure of the HOX locus. The presence of non-coding RNAs, embedded within the HOX cluster, and the role of these molecules in breast cancer have been reviewed. We further evaluate the characteristic activity of HOX protein in breast cancer and its therapeutic potential.

scholarly journals Estimating intrafraction tumor motion during fiducial-based liver stereotactic radiotherapy via an iterative closest point (ICP) algorithm

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Wu-zhou Li ◽  
Zhi-wen Liang ◽  
Yi Cao ◽  
Ting-ting Cao ◽  
Hong Quan ◽  
...  
Keyword(s):  
Stereotactic Radiotherapy ◽  
Imaging System ◽  
Liver Tumors ◽  
Three Dimensional ◽  
Rigid Motion ◽  
Iterative Closest Point ◽  
Tumor Motion ◽  
Tracking Accuracy ◽  
Icp Algorithm ◽  
Anterior Posterior

Abstract Background Tumor motion may compromise the accuracy of liver stereotactic radiotherapy. In order to carry out a precise planning, estimating liver tumor motion during radiotherapy has received a lot of attention. Previous approach may have difficult to deal with image data corrupted by noise. The iterative closest point (ICP) algorithm is widely used for estimating the rigid registration of three-dimensional point sets when these data were dense or corrupted. In the light of this, our study estimated the three-dimensional (3D) rigid motion of liver tumors during stereotactic liver radiotherapy using reconstructed 3D coordinates of fiducials based on the ICP algorithm. Methods Four hundred ninety-five pairs of orthogonal kilovoltage (KV) images from the CyberKnife stereo imaging system for 12 patients were used in this study. For each pair of images, the 3D coordinates of fiducial markers inside the liver were calculated via geometric derivations. The 3D coordinates were used to calculate the real-time translational and rotational motion of liver tumors around three axes via an ICP algorithm. The residual error was also investigated both with and without rotational correction. Results The translational shifts of liver tumors in left-right (LR), anterior-posterior (AP),and superior-inferior (SI) directions were 2.92 ± 1.98 mm, 5.54 ± 3.12 mm, and 16.22 ± 5.86 mm, respectively; the rotational angles in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were 3.95° ± 3.08°, 4.93° ± 2.90°, and 4.09° ± 1.99°, respectively. Rotational correction decreased 3D fiducial displacement from 1.19 ± 0.35 mm to 0.65 ± 0.24 mm (P<0.001). Conclusions The maximum translational movement occurred in the SI direction. Rotational correction decreased fiducial displacements and increased tumor tracking accuracy.

scholarly journals Hox dosage contributes to flight appendage morphology in Drosophila

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rachel Paul ◽  
Guillaume Giraud ◽  
Katrin Domsch ◽  
Marilyne Duffraisse ◽  
Frédéric Marmigère ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Differential Expression ◽  
Hox Genes ◽  
Expression Profiles ◽  
Fruit Fly ◽  
Insect Species ◽  
Wing Morphology ◽  
Hox Proteins ◽  
Spatial Expression ◽  
Flying Insects

AbstractFlying insects have invaded all the aerial space on Earth and this astonishing radiation could not have been possible without a remarkable morphological diversification of their flight appendages. Here, we show that characteristic spatial expression profiles and levels of the Hox genes Antennapedia (Antp) and Ultrabithorax (Ubx) underlie the formation of two different flight organs in the fruit fly Drosophila melanogaster. We further demonstrate that flight appendage morphology is dependent on specific Hox doses. Interestingly, we find that wing morphology from evolutionary distant four-winged insect species is also associated with a differential expression of Antp and Ubx. We propose that variation in the spatial expression profile and dosage of Hox proteins is a major determinant of flight appendage diversification in Drosophila and possibly in other insect species during evolution.

scholarly journals Hox genes are essential for the development of eyespots in Bicyclus anynana butterflies

Genetics ◽  
2020 ◽  
Vol 217 (1) ◽  
Author(s):  
Yuji Matsuoka ◽  
Antónia Monteiro
Keyword(s):  
Hox Genes ◽  
Bicyclus Anynana ◽  
Hox Gene ◽  
Novel Traits ◽  
Anterior Posterior ◽  
Anterior Posterior Axis

Abstract The eyespot patterns found on the wings of nymphalid butterflies are novel traits that originated first in hindwings and subsequently in forewings, suggesting that eyespot development might be dependent on Hox genes. Hindwings differ from forewings in the expression of Ultrabithorax (Ubx), but the function of this Hox gene in eyespot development as well as that of another Hox gene Antennapedia (Antp), expressed specifically in eyespots centers on both wings, are still unclear. We used CRISPR-Cas9 to target both genes in Bicyclus anynana butterflies. We show that Antp is essential for eyespot development on the forewings and for the differentiation of white centers and larger eyespots on hindwings, whereas Ubx is essential not only for the development of at least some hindwing eyespots but also for repressing the size of other eyespots. Additionally, Antp is essential for the development of silver scales in male wings. In summary, Antp and Ubx, in addition to their conserved roles in modifying serially homologous segments along the anterior–posterior axis of insects, have acquired a novel role in promoting the development of a new set of serial homologs, the eyespot patterns, in both forewings (Antp) and hindwings (Antp and Ubx) of B. anynana butterflies. We propose that the peculiar pattern of eyespot origins on hindwings first, followed by forewings, could be due to an initial co-option of Ubx into eyespot development followed by a later, partially redundant, co-option of Antp into the same network.

scholarly journals The patellofemoral morphology and the normal predicted value of tibial tuberosity-trochlear groove distance in the Chinese population

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhe Li ◽  
Guanzhi Liu ◽  
Run Tian ◽  
Ning Kong ◽  
Yue Li ◽  
...  
Keyword(s):  
Individual Differences ◽  
Chinese Population ◽  
Pearson Correlation ◽  
Three Dimensional ◽  
Correlation Coefficients ◽  
Tibial Tuberosity ◽  
Trochlear Groove ◽  
Lasso Regression ◽  
Cross Sectional ◽  
Anterior Posterior

Abstract Background Our objective was to obtain normal patellofemoral measurements to analyse sex and individual differences. In addition, the absolute values and indices of tibial tuberosity-trochlear groove (TT-TG) distances are still controversial in clinical application. A better method to enable precise prediction is still needed. Methods Seventy-eight knees of 78 participants without knee pathologies were included in this cross-sectional study. A CT scan was conducted for all participants and three-dimensional knee models were constructed using Mimics and SolidWorks software. We measured and analysed 19 parameters including the TT-TG distance and dimensions and shapes of the patella, femur, tibia, and trochlea. LASSO regression was used to predict the normal TT-TG distances. Results The dimensional parameters, TT-TG distance, and femoral aspect ratio of the men were significantly larger than those of women (all p values < 0.05). However, after controlling for the bias from age, height, and weight, there were no significant differences in TT-TG distances and anterior-posterior dimensions between the sexes (all p values > 0.05). The Pearson correlation coefficients between the anterior femoral offset and other indexes were consistently below 0.3, indicating no relationship or a weak relationship. Similar results were observed for the sulcus angle and the Wiberg index. Using LASSO regression, we obtained four parameters to predict the TT-TG distance (R2 = 0.5612, p < 0.01) to achieve the optimal accuracy and convenience. Conclusions Normative data of patellofemoral morphology were provided for the Chinese population. The anterior-posterior dimensions of the women were thicker than those of men for the same medial-lateral dimensions. More attention should be paid to not only sex differences but also individual differences, especially the anterior condyle and trochlea. In addition, this study provided a new method to predict TT-TG distances accurately.

scholarly journals HiChIP and Hi-C Protocol Optimized for Primary Murine T Cells

2021 ◽  
Vol 4 (3) ◽  
pp. 49
Author(s):  
Tomas Zelenka ◽  
Charalampos Spilianakis
Keyword(s):  
T Cells ◽  
Long Range ◽  
Three Dimensional ◽  
Cell Types ◽  
Range Interaction ◽  
Chromatin Interactions ◽  
Optimized Protocol ◽  
Long Range Interaction ◽  
Chromatin Compactness ◽  
Detailed Protocol

The functional implications of the three-dimensional genome organization are becoming increasingly recognized. The Hi-C and HiChIP research approaches belong among the most popular choices for probing long-range chromatin interactions. A few methodical protocols have been published so far, yet their reproducibility and efficiency may vary. Most importantly, the high frequency of the dangling ends may dramatically affect the number of usable reads mapped to valid interaction pairs. Additionally, more obstacles arise from the chromatin compactness of certain investigated cell types, such as primary T cells, which due to their small and compact nuclei, impede limitations for their use in various genomic approaches. Here we systematically optimized all the major steps of the HiChIP protocol in T cells. As a result, we reduced the number of dangling ends to nearly zero and increased the proportion of long-range interaction pairs. Moreover, using three different mouse genotypes and multiple biological replicates, we demonstrated the high reproducibility of the optimized protocol. Although our primary goal was to optimize HiChIP, we also successfully applied the optimized steps to Hi-C, given their significant protocol overlap. Overall, we describe the rationale behind every optimization step, followed by a detailed protocol for both HiChIP and Hi-C experiments.

The Effect of Lifting vs. Lowering on Spinal Loading

1996 ◽  
Vol 40 (13) ◽  
pp. 599-603 ◽  
Author(s):  
Kermit G. Davis
Keyword(s):  
Muscle Activity ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Muscle Forces ◽  
Shear Forces ◽  
Spinal Loading ◽  
Spinal Loads ◽  
Trunk Strength ◽  
Anterior Posterior ◽  
Three Dimensional Space

In industry, workers perform tasks requiring both lifting and lowering. During concentric lifting, the muscles are shortening as the force is being generated. Conversely, the muscle lengthens while generating force during eccentric lowering. While research on various lifting tasks is extensive, there has been limited research performed to evaluate the lowering tasks. Most of the research that does exist on lowering has investigated muscle activity and trunk strength. None of these studies have investigated spinal loading. The current study estimated the effects of lifting and lowering on spinal loads and predicted moments imposed on the spine. Ten subjects performed both eccentric and concentric lifts under sagittally symmetric conditions. The tasks were performed under isokinetic trunk velocities of 5, 10, 20, 40, and 80 deg/s while holding a box with weights of 9.1, 18.2, and 27.3 kg. Spinal loads and predicted moments in three dimensional space were estimated by an EMG-assisted model which has been adjusted to incorporate the artifacts of eccentric lifting. Eccentric strength was found to be 56 percent greater than during concentric lifting. The lowering tasks produced significantly higher compression forces but lower anterior-posterior shear forces than the concentric lifting tasks. The differences in the spinal loads between the two lifting tasks were attributed to the internal muscle forces and unequal moments resulting from differences in the lifting path of the box. Thus, the differences between the lifting tasks resulted from different lifting styles associated with eccentric and concentric movements

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