The key to development: interpreting the histone code?

E2F target genes: unraveling the biology.

During vertebrate development, clustered genes from the Hox family of transcription factors are activated in a precise temporal and spatial sequence that follows their chromosomal order (the "Hox clock"). Recent advances in the knowledge of the underlying mechanisms reveal that the embryo uses a variety of strategies to implement this colinear process, depending on both the type and the evolutionary history of axial structures. The search for a universal mechanism has likely hampered our understanding of this enigmatic phenomenon, which may be caused by various and unrelated regulatory processes, as long as the final distribution of proteins (the HOX code) is preserved.

https://science.sciencemag.org/content/sci/301/5631/331.full.pdf

Organizing Axes in Time and Space; 25 Years of Colinear Tinkering

The highly homologous Rnf2 (Ring1b) and Ring1 (Ring1a) proteins were identified as in vivo interactors of the Polycomb Group (PcG) protein Bmi1. Functional ablation of Rnf2 results in gastrulation arrest, in contrast to relatively mild phenotypes in most other PcG gene null mutants belonging to the same functional group, among which is Ring1. Developmental defects occur in both embryonic and extraembryonic tissues during gastrulation. The early lethal phenotype is reminiscent of that of the PcG-gene knockouts Eed and Ezh2, which belong to a separate functional PcG group and PcG protein complex. This finding indicates that these biochemically distinct PcG complexes are both required during early mouse development. In contrast to the strong skeletal transformation in Ring1 hemizygous mice, hemizygocity for Rnf2 does not affect vertebral identity. However, it does aggravate the cerebellar phenotype in a Bmi1 null-mutant background. Together, these results suggest that Rnf2 or Ring1-containing PcG complexes have minimal functional redundancy in specific tissues, despite overlap in expression patterns. We show that the early developmental arrest in Rnf2-null embryos is partially bypassed by genetic inactivation of the Cdkn2a (Ink4a/ARF) locus. Importantly, this finding implicates Polycomb-mediated repression of the Cdkn2a locus in early murine development.

https://www.pnas.org/content/pnas/100/5/2468.full.pdf

Rnf2 (Ring1b) deficiency causes gastrulation arrest and cell cycle inhibition

The axial skeleton in all vertebrates is composed of similar components that extend from anterior to posterior along the body axis: the occipital skull bones and cervical, thoracic, lumbar, sacral, and caudal vertebrae. Despite significant changes in the number and size of these elements during evolution, the basic character of these anatomical elements, as well as the order in which they appear in vertebrate skeletons, have remained remarkably similar. Through extensive expression analyses, classic morphological perturbation experiments in chicken and targeted loss-of-function analyses in mice, Hox genes have proven to be critical regulators in the establishment of axial skeleton morphology. The convergence of these studies to date allows an emerging understanding of Hox gene function in patterning the vertebrate axial skeleton. This review summarizes genetic and embryologic findings regarding the role of Hox genes in establishing axial morphology and how these combined results impact our current understanding of the vertebrate Hox code. Developmental Dynamics 236:2454 –2463, 2007. © 2007 Wiley-Liss, Inc.

/pdf/hox-patterning-of-the-vertebrate-axial-skeleton-20bbvehlmd.pdf

Hox patterning of the vertebrate axial skeleton.

Spatially and temporally restricted expression of the Hox genes along the main and appendicular axes is essential for correct patterning of vertebrate embryos. In this overview we discuss the latest data that shed light on the mechanisms underlying the generation of the expression domains of the Hox genes. The molecular genetic interactions governing initial transcription of the Hox genes in the posterior part of the primitive streak during mouse and chick gastrulation remain enigmatic. But the recent discovery by Kondo and Duboule (Cell, 97, 1999, 407-417) of a "cluster repressive regulation", will undoubtedly lead to a better understanding of the molecular genetic mechanism underlying colinear and sequential initiation of Hox gene transcription. Recently progress has been booked in characterizing the basal processes driving progression of the Hox expression domains during their establishment. Hox expression is still labile while being established. The transcriptional state of Hox genes in anterior tissues can be reprogrammed under the influence of more posterior locations. Posteriorizing activity may involve RA and FGF signaling. It is only when these interactions and, in some cases at least, regulatory interactions with Hox and cdx gene products occur appropriately, that the Hox expression domains would be correctly established. After the Hox expression domains have been established, regulatory processes involving the products of Polycomb and trithorax- Group genes start operating, perpetuating the transcriptional state of the Hox genes within and outside the expression domains. Whether control at the level of chromatin structure, believed to operate during the late maintenance phase of Hox gene expression, is also involved in regulating concerted initial expression of these genes, is a possibility that has been suggested.

/pdf/initiation-establishment-and-maintenance-of-hox-gene-4epr4iijgy.pdf

Initiation, establishment and maintenance of Hox gene expression patterns in the mouse.

Hox genes have been shown to play a key role in the acquisition of positional identity by precursors of embryonic axial, paraxial and limb structures. This function is thought to depend on the sequential, concerted expression of these genes in time and space. However the underlying molecular mechanisms of this collinear expression are still largely unknown. So far we had identified proximal regulatory elements driving expression of Hoxb-8/LacZ transgenes in Hox-like expression patterns with rostral boundaries more posterior than those of the endogenous gene. In this work we have analyzed 30 kb of 3' genomic sequences for Hoxb-8 regulatory activity in transgenic mice. We have identified a control region in the Hoxb-5/b-4 intergenic region that rostrally extends the Hoxb-8/LacZ expression domain into the posterior hindbrain. In combination with the Hoxb-8 minimal promoter, the 3' control region drives transgene expression with boundaries more anterior than those of Hoxb-8 in the neural tube. When combined with a 4.5 kb Hoxb-8 upstream sequence, where essential proximal regulatory sequences are located, the 3' control region drives transgene expression in a domain which seems to correspond to that of the endogenous Hoxb-8. By deletion analysis we have narrowed down to 550bp the regulatory activity interacting with the Hoxb-8 minimal promoter. We discuss the possibility that this remote 3' enhancer, which is the closest regulatory region found in the cluster to rostrally extend Hoxb-8/LacZ expression, could be involved in the regulation of Hoxb-8 and interact with the proximal control elements.

/pdf/a-3-remote-control-region-is-a-candidate-to-modulate-hoxb-8-4450naostv.pdf

A 3' remote control region is a candidate to modulate Hoxb-8 expression boundaries.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

W de Graaff

Author Tools

Chat about Author

Papers

Initiation, establishment and maintenance of Hox gene expression patterns in the mouse.

A 3' remote control region is a candidate to modulate Hoxb-8 expression boundaries.