“REWIRING STEM CELLS: NEW TECHNIQUE MAY REVOLUTIONIZE UNDERSTANDING OF HOW GENES FUNCTION” AND “IMPORTANT DISCOVERY FOR DIAGNOSIS OF GENETIC DISEASES”. “REWIRING STEM CELLS: NEW TECHNIQUE MAY REVOLUTIONIZE UNDERSTANDING OF HOW GENES FUNCTION” AND “IMPORTANT DISCOVERY FOR DIAGNOSIS OF GENETIC DISEASES”. María Angélica Díaz Uribe Medicine student III Semester Molecular Biology

INTRODUCTION news report on genetic studies about effective method to identify the working of genes in cell differentiation and possible causes of genetic syndromes attributed to the three-dimensional organization of chromatin.

“REWIRING STEM CELLS: NEW TECHNIQUE MAY REVOLUTIONIZE UNDERSTANDING OF HOW GENES FUNCTION”

Cell type in an organism expresses a subset of all the genes that constitute the genome of that species. Each cell type is defined by its particular pattern of regulated gene expression. Cell differentiation is thus a transition of a cell from one cell type to another and it involves a switch from one pattern of gene expression to another. Cellular differentiation during development can be understood as the result of a gene regulatory network.

“REWIRING STEM CELLS: NEW TECHNIQUE MAY REVOLUTIONIZE UNDERSTANDING OF HOW GENES FUNCTION” Haploid cells show all of the same characteristics as stem cells with two sets of chromosomes, and retain the same full developmental potential. This cells facilitates that the process is a bit faster. The searches used unfertilised mouse eggs to generate embryonic stem cells with a single set of chromosomes, known as haploid stem cells.

“REWIRING STEM CELLS: NEW TECHNIQUE MAY REVOLUTIONIZE UNDERSTANDING OF HOW GENES FUNCTION” The researchers used transposons -- "jumping genes"- to make mutations in nearly all genes. The effect of a mutation can be seen immediately in haploid cells because there is no second gene copy. A transposable element (TE, transposon or retrotransposo n) is a DNA sequence that can change its position within the genome, sometimes creating or reversing mutations and altering the cell's genome size. Transposition often results in duplication of the TE

Identify key players regulating exit from self-renewal in ESCs using a forward genetic screen in haploid ESCs. “REWIRING STEM CELLS: NEW TECHNIQUE MAY REVOLUTIONIZE UNDERSTANDING OF HOW GENES FUNCTION” They used haploid ESCs to develop a forward genetics screen for pluripotency regulators. A cohort of candidate genes that promote collapse of self-renewal was validated. The conserved zinc finger protein Zfp706 promotes differentiation. Pum1 mediates posttranscriptional destabilization of the pluripotency network. METHODS

Circuits self-renewal of embryonic stem cells (ESCs) haploid is a useful and fast tool for determining the operational work of the gene, this discovery opens the door for intervention in the development process and makes possible the understanding of a large number heart disease, liver problems and cancer. PERSONAL OBSERVATION “REWIRING STEM CELLS: NEW TECHNIQUE MAY REVOLUTIONIZE UNDERSTANDING OF HOW GENES FUNCTION”

“IMPORTANT DISCOVERY FOR DIAGNOSIS OF GENETIC DISEASES”.

The substance distributed in the nucleus of a cell that condenses to form chromosomes during cell division. The basic repeating structural (and functional) unit of chromatin is the nucleosome, which contains nine histone proteins and about 166 base pairs of DNA “IMPORTANT DISCOVERY FOR DIAGNOSIS OF GENETIC DISEASES”. activity of genes controlling embryonic development The three- dimensional organization of the chromatin.

Hox genes encode transcription factors with crucial roles during development. These genes are grouped in four different clusters names HoxA, B, C, and D. Mutations in genes of the HoxAand D clusters have been found in several human syndromes, affecting in some cases limb development. “IMPORTANT DISCOVERY FOR DIAGNOSIS OF GENETIC DISEASES”.

Enhancer In genetics, an enhancer is a short region of DNA that can be bound with proteins (namely, the trans-acting factors, much like a set of transcription factors) to enhance transcription levels of genes (hence the name) in a gene cluster. While enhancers are usually cis- acting, an enhancer does not need to be particularly close to the genes it acts on, and sometimes need not be located on the same chromosome

“IMPORTANT DISCOVERY FOR DIAGNOSIS OF GENETIC DISEASES”. Model illustrating how genome topology underlies the tissue-specific regulation of HoxA genes. The HoxA cluster is partitioned between two TADs (light blue), physically segregating3′HoxA from 5′HoxA genes in a mostly cell-type independent manner. In contrast, the sub-TAD interaction pattern is drastically different in the limb (A) compared to the head (B).

“IMPORTANT DISCOVERY FOR DIAGNOSIS OF GENETIC DISEASES”. PERSONAL OBSERVATION The study reveals that extensive three- dimensional chromatin interactions control the expression of HoxA genes in developing limbs by forming distinct topological domains containing limb enhancers, which interact with each other and with the topological domains containing their target genes.

MEDICAL UTILITY

Achieve a better understanding of cell differentiation process is essential for the future of genetic research and therefore, for medical progress in search of fighting diseases current. studies on the structure and organization of chromatin are the beginning to identify the source of many genetic diseases and manipulate the genes involved to prevent.

BIBLIOGRAPHY Rewiring stem cells: New technique may revolutionize understanding of how genes function, Science Daily; 2014 [cited 2014 january 9]. Available at: Important discovery for diagnosis of genetic diseases. Science Daily; 2014 [january 16]. Available at: Leeb M, Dietmann S, Paramor M, Niwa H, Smith A.(2014). Genetic Exploration of the Exit from Self-Renewal Using Haploid Embryonic Stem Cells. Cell Stem Cell [online]. Availabe at: Exploration of the Exit from Self-Renewal Using Haploid Embryonic Stem Cells Soizik Berlivet, Denis Paquette, Annie Dumouchel,David Langlais, Josée Dostie, & Marie Kmita. (2014).Clustering of Tissue-Specific Sub-TADs Accompanies the Regulation of HoxAGenes in Developing Limbs. PloS Genetics [online] Available at:

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