Developmental and spatial patterns of expression of the mouse homeobox gene, Hox 2.1

The Hox 2.1 gene forms part of a cluster of homeobox-containing genes on mouse chromosome 11. Analysis of Hox 2.1 cDNAs isolated from an 8 1/2-day p.c. mouse embryo library predicts that the gene encodes a 269 amino acid protein (Mr, 29,432). This deduced protein contains a homeobox 15 amino acids from the carboxy terminus and is very rich in serine and proline. A second partially conserved region present in several other genes containing homeoboxes, the hexapeptide Ile-Phe-Pro-Trp-Met-Arg, is located 12 amino acids upstream of the homeodomain and is encoded by a separate exon. Analysis of Hox 2.1 gene expression reveals a complex and tissue-specific series of RNA transcripts in a broad range of fetal tissues (lung, spinal cord, kidney, gut, spleen, liver and visceral yolk sac). Comparison of the temporal patterns of gene expression during development and in the adult suggests that Hox 2.1 is regulated independently in different tissues. Evidence is also presented that transcripts from other loci have extensive homology to the Hox 2.1 gene in sequences outside of the homeobox. In situ hybridization shows that Hox 2.1 transcripts are regionally localized in the spinal cord in an apparent anterior-posterior gradient extending from the hind brain. The distribution of RNA also displays a cell-type specificity in the lung, where mesodermal cells surrounding the branching epithelial cell layer accumulate high levels of Hox 2.1 transcripts.

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Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1716032115 ◽

2017 ◽

Vol 115 (2) ◽

pp. E302-E309 ◽

Cited By ~ 75

Author(s):

Noriko Itoh ◽

Yuichiro Itoh ◽

Alessia Tassoni ◽

Emily Ren ◽

Max Kaito ◽

...

Keyword(s):

Gene Expression ◽

Multiple Sclerosis ◽

Spinal Cord ◽

Cholesterol Synthesis ◽

Neurological Diseases ◽

Cell Types ◽

Specific Gene ◽

Bioinformatics Analyses ◽

Pathway Gene ◽

A Cell

Changes in gene expression that occur across the central nervous system (CNS) during neurological diseases do not address the heterogeneity of cell types from one CNS region to another and are complicated by alterations in cellular composition during disease. Multiple sclerosis (MS) is multifocal by definition. Here, a cell-specific and region-specific transcriptomics approach was used to determine gene expression changes in astrocytes in the most widely used MS model, experimental autoimmune encephalomyelitis (EAE). Astrocyte-specific RNAs from various neuroanatomic regions were attained using RiboTag technology. Sequencing and bioinformatics analyses showed that EAE-induced gene expression changes differed between neuroanatomic regions when comparing astrocytes from spinal cord, cerebellum, cerebral cortex, and hippocampus. The top gene pathways that were changed in astrocytes from spinal cord during chronic EAE involved decreases in expression of cholesterol synthesis genes while immune pathway gene expression in astrocytes was increased. Optic nerve from EAE and optic chiasm from MS also showed decreased cholesterol synthesis gene expression. The potential role of cholesterol synthesized by astrocytes during EAE and MS is discussed. Together, this provides proof-of-concept that a cell-specific and region-specific gene expression approach can provide potential treatment targets in distinct neuroanatomic regions during multifocal neurological diseases.

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Evidence from oyster suggests an ancient role for Pdx in regulating insulin gene expression in animals

Nature Communications ◽

10.1038/s41467-021-23216-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Fei Xu ◽

Ferdinand Marlétaz ◽

Daria Gavriouchkina ◽

Xiao Liu ◽

Tatjana Sauka-Spengler ◽

...

Keyword(s):

Gene Expression ◽

Regulatory Element ◽

Expression Patterns ◽

Homeobox Gene ◽

Gene Interaction ◽

Binding Interaction ◽

Upstream Regulatory Element ◽

A Cell ◽

Insulin Gene Expression ◽

Cell Culture Assay

AbstractHox and ParaHox genes encode transcription factors with similar expression patterns in divergent animals. The Pdx (Xlox) homeobox gene, for example, is expressed in a sharp spatial domain in the endodermal cell layer of the gut in chordates, echinoderms, annelids and molluscs. The significance of comparable gene expression patterns is unclear because it is not known if downstream transcriptional targets are also conserved. Here, we report evidence indicating that a classic transcriptional target of Pdx1 in vertebrates, the insulin gene, is a likely direct target of Pdx in Pacific oyster adults. We show that one insulin-related gene, cgILP, is co-expressed with cgPdx in oyster digestive tissue. Transcriptomic comparison suggests that this tissue plays a similar role to the vertebrate pancreas. Using ATAC-seq and ChIP, we identify an upstream regulatory element of the cgILP gene which shows binding interaction with cgPdx protein in oyster hepatopancreas and demonstrate, using a cell culture assay, that the oyster Pdx can act as a transcriptional activator through this site, possibly in synergy with NeuroD. These data argue that a classic homeodomain-target gene interaction dates back to the origin of Bilateria.

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Motoneuron fate specification revealed by patterned LIM homeobox gene expression in embryonic zebrafish

Development ◽

10.1242/dev.121.12.4117 ◽

1995 ◽

Vol 121 (12) ◽

pp. 4117-4125 ◽

Cited By ~ 37

Author(s):

B. Appel ◽

V. Korzh ◽

E. Glasgow ◽

S. Thor ◽

T. Edlund ◽

...

Keyword(s):

Gene Expression ◽

Spinal Cord ◽

Gene Transcription ◽

Cell Body ◽

Homeobox Genes ◽

Homeobox Gene ◽

Positional Information ◽

Axonal Projection ◽

Fate Specification ◽

Genes Expression

In zebrafish, individual primary motoneurons can be uniquely identified by their characteristic cell body positions and axonal projection patterns. The fate of individual primary motoneurons remains plastic until just prior to axogenesis when they become committed to particular identities. We find that distinct primary motoneurons express particular combinations of LIM homeobox genes. Expression precedes axogenesis as well as commitment, suggesting that LIM homeobox genes may contribute to the specification of motoneuronal fates. By transplanting them to new spinal cord positions, we demonstrate that primary motoneurons can initiate a new program of LIM homeobox gene expression, as well as the morphological features appropriate for the new position. We conclude that the patterned distribution of different primary motoneuronal types within the zebrafish spinal cord follows the patterned expression of LIM homeobox genes, and that this reflects a highly resolved system of positional information controlling gene transcription.

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Visualization and sequencing of accessible chromatin reveals cell cycle and post romidepsin treatment dynamics

10.1101/2020.04.27.064691 ◽

2020 ◽

Author(s):

Pierre-Olivier Estève ◽

Udayakumar S. Vishnu ◽

Hang Gyeong Chin ◽

Sriharsa Pradhan

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Histone Deacetylases ◽

Mammalian Cells ◽

Chromatin Accessibility ◽

Cell Type Specificity ◽

Myc Oncogene ◽

Genome Wide ◽

A Cell ◽

Accessible Chromatin

AbstractChromatin accessibility is a predictor of gene expression, cell division and cell type specificity. NicE-viewSeq (Nicking Enzyme assisted viewing and Sequencing) allows accessible chromatin visualization and sequencing with overall lower mitochondrial DNA and duplicated sequences interference relative to ATAC-see. Using NicE-viewSeq, we interrogated the accessibility of chromatin in a cell cycle (G1, S and G2/M) - specific manner using mammalian cells. Despite DNA replication and subsequent condensation of chromatin to chromosomes, chromatin accessibility remained generally preserved with minimal subtle alterations. Genome-wide alteration of chromatin accessibility within TSS and enhancer elements gradually decreased as cells progressed from G1 to G2M, with distinct differential accessibility near consensus transcription factors sites. Inhibition of histone deacetylases promoted accessible chromatin within gene bodies, correlating with apoptotic gene expression. In addition, reduced chromatin accessibility for the MYC oncogene pathway correlated with down regulation of pertinent genes. Surprisingly, repetitive RNA loci expression remained unaltered following histone acetylation-mediated increased accessibility. Therefore, we suggest that subtle changes in chromatin accessibility is a prerequisite during cell cycle and histone deacetylase inhibitor mediated therapeutics.

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Nutrient-regulated gene expression in eukaryotes

Biochemical Society Symposium ◽

10.1042/bss0730085 ◽

2006 ◽

Vol 73 ◽

pp. 85-96 ◽

Cited By ~ 8

Author(s):

Richard J. Reece ◽

Laila Beynon ◽

Stacey Holden ◽

Amanda D. Hughes ◽

Karine Rébora ◽

...

Keyword(s):

Gene Expression ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Transcriptional Control ◽

Direct Interaction ◽

Signalling Pathways ◽

A Cell ◽

One Step ◽

Higher Eukaryotes ◽

Regulated Gene Expression

The recognition of changes in environmental conditions, and the ability to adapt to these changes, is essential for the viability of cells. There are numerous well characterized systems by which the presence or absence of an individual metabolite may be recognized by a cell. However, the recognition of a metabolite is just one step in a process that often results in changes in the expression of whole sets of genes required to respond to that metabolite. In higher eukaryotes, the signalling pathway between metabolite recognition and transcriptional control can be complex. Recent evidence from the relatively simple eukaryote yeast suggests that complex signalling pathways may be circumvented through the direct interaction between individual metabolites and regulators of RNA polymerase II-mediated transcription. Biochemical and structural analyses are beginning to unravel these elegant genetic control elements.

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