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The organization of DNA into chromatin is dynamic; nucleosomes are frequently displaced to facilitate the ability of regulatory proteins to access specific DNA elements. To gain insight into nucleosome dynamics, and to follow how dynamics change during differentiation, we used a technique called time-ChIP to quantitatively assess histone H3.3 turnover genome-wide during differentiation of mouse ESCs. We found that, without prior assumptions, high turnover could be used to identify regions involved in gene regulation. High turnover was seen at enhancers, as observed previously, with particularly high turnover at super-enhancers. In contrast, regions associated with the repressive Polycomb-Group showed low turnover in ESCs. Turnover correlated with DNA accessibility. Upon differentiation, numerous changes in H3.3 turnover rates were observed, the majority of which occurred at enhancers. Thus, time-ChIP measurement of histone turnover shows that active enhancers are unusually dynamic in ESCs and changes in highly dynamic nucleosomes predominate at enhancers during differentiation. In animal, plant and other eukaryotic cells, DNA wraps around histone proteins to form structures called nucleosomes. This compacts long strands of DNA to fit them inside a cell. However, nucleosomes also act as barriers that can prevent access to the DNA. This affects the activity, or “expression”, of genes because gene expression requires proteins called transcription factors to bind to specific DNA regions. Therefore, nucleosomes must be disrupted or removed in order to access their DNA and allow their genes to be expressed. Transcription factors can bind to DNA sequences called enhancers to activate nearby genes. Groups of enhancers, called super-enhancers, also exist to further bolster the activity of certain genes, particularly those involved in determining cell identity. Recent work has shown that nucleosomes are frequently lost and then replaced by new ones (in a process referred to as turnover) in DNA regions that include enhancers. Measuring the rate of turnover of nucleosomes can thus provide information about which DNA regions regulate gene expression. Embryonic stem cells can transform or “differentiate” into any type of cell in the body. During this transformation process, different genes are switched on or off in the cell in order to give it a new identity. It is not known how nucleosome turnover changes when this happens. Deaton et al. have now developed a new method called time-ChIP that can measure the rate of nucleosome turnover across the entire DNA of a cell. Using this technique to analyze mouse embryonic stem cells revealed that nucleosome turnover occurs rapidly at enhancers. Furthermore, nucleosomes at super-enhancers are particularly dynamic and turn over more quickly than in any other DNA region. Deaton et al. next analyzed how turnover changes after the mouse embryonic stem cells have developed into neural stem cells. This revealed that the regions of DNA where high turnover occurs change as the cells differentiate, in part because this transformation activates a different set of enhancers. However, the most rapid turnover still takes place at enhancers. Overall, these observations suggest that the high rate of nucleosome turnover at enhancers makes DNA accessible to transcription factors. The next step is to use the new time-ChIP method to study how nucleosome turnover changes during the processes that pattern gene expression as an animal develops from an embryo.

Kinetochores assemble on distinct ‘centrochromatin’ containing the histone H3 variant CENP‐A and interspersed nucleosomes dimethylated on H3K4 (H3K4me2). Little is known about how the chromatin environment at active centromeres governs centromeric structure and function. Here, we report that centrochromatin resembles K4–K36 domains found in the body of some actively transcribed housekeeping genes. By tethering the lysine‐specific demethylase 1 (LSD1), we specifically depleted H3K4me2, a modification thought to have a role in transcriptional memory, from the kinetochore of a synthetic human artificial chromosome (HAC). H3K4me2 depletion caused kinetochores to suffer a rapid loss of transcription of the underlying α‐satellite DNA and to no longer efficiently recruit HJURP, the CENP‐A chaperone. Kinetochores depleted of H3K4me2 remained functional in the short term, but were defective in incorporation of CENP‐A, and were gradually inactivated. Our data provide a functional link between the centromeric chromatin, α‐satellite transcription, maintenance of CENP‐A levels and kinetochore stability. Here, centromeric histone marks on a human artificial chromosome are found to resemble the chromatin landscape in transcribed genes, and selective manipulation shows them to govern the incorporation of the centromere‐specifying CENP‐A histone variant.

RESUMEN. Antecedentes: El gen noggin  (Nog) es uno de los antagonistas de las proteínas morfogénicas óseas (BMPs)  y tiene como función modular la señal de estas. Cuando su acción no es efectiva, ocurre una actividad excesiva de las BMPs que causa serias anormalidades en el desarrollo. Estudios han demostrado que Nog es crítico para la condrogénesis, osteogénesis y formación de las articulaciones y parece estar involucrado con el crecimiento de estructuras craneofaciales, entre ellas, la mandíbula. Existen en la literatura pocos estudios acerca de la relación entre Nog  y su papel en el desarrollo mandibular. Objetivo: Esta revisión hace una descripción de  los factores moleculares que intervienen en la formación de la mandíbula. Se hace un énfasis principalmente en las BMPs, su función, vía de señalización y cómo Nog regula esta vía, para conducir a  formular una  hipótesis del posible papel de este gen en el desarrollo mandibular y cómo su alteración podría llegar a causar el micrognatismo mandibular.ABSTRACT. Background: Noggin (Nog) gene is one of the antagonists of bone morphogenic proteins (BMPs) and its function is to modulate the signs. When Nog’s action is ineffective, an excessive activity of BMPs occur causing serious developmental abnormalities. Studies have shown that Nog is critical for chondrogenesis, osteogenesis, and joint training and appears to be involved in the growth of craniofacial structures, including the jaw. There are in the literature, few studies about the relationship between Nog and its role in the mandibular development. Purpose: This article reviews the molecular factors involved in the jaw development, focusing primarily on BMPs, their function, signaling pathway as Nog regulates this path. It leads to hypothesize the Nog’s possible role on the mandibular development and how its alteration can cause mandibular micrognatism.RESUMO. Antecedente: O gene Noggin (Nog) é um dos antagonistas das proteínas morfogênicas ósseas (BMPs) e tem como função modular o sinal das mesmas. Quando sua ação não é efetiva, ocorre uma atividade excessiva das BMPs causando sérias anormalidades no desenvolvimento. Estudos veem demonstrando que Nog é essencial para a condrogênesis, osteogênesis, formação das articulações e parece estar envolvido com o crescimento de estruturas craniofaciais, incluindo a mandíbula. Na literatura há poucos estudos sobre a relação entre Nog e seu papel no desenvolvimento mandibular. Objetivo: Esta revisão fornece uma descrição do desenvolvimento da mandíbula, os fatores moleculares envolvidos na sua formação, com ênfases principalmente nas BMPs, sua função, via de sinalização e como Nog regula esta via, levando-nos a formular uma hipóteses do possível papel de Nog no desenvolvimento mandibular e como sua alteração poderia causar micrognatismo mandibular. 

Cell proliferation and differentiation into distinct cell types during development requires the preservation of cellular phenotypes during cell divisions. How the cell maintains its identity and how cells with the same genetic information display different heritable phenotypes or gene expression profiles are fundamental questions in biology. The mitotic and/or meiotic inheritance of changes in gene expression that are not due to changes in DNA sequences is known as epigenetic inheritance.

Antecedentes: El gen noggin  (Nog) es uno de los antagonistas de las proteínas morfogénicas óseas (BMPs)  y tiene como función modular la señal de estas. Cuando su acción no es efectiva, ocurre una actividad excesiva de las BMPs que causa serias anormalidades en el desarrollo. Estudios han demostrado que Nog es crítico para la condrogénesis, osteogénesis y formación de las articulaciones y parece estar involucrado con el crecimiento de estructuras craneofaciales, entre ellas, la mandíbula. Existen en la literatura pocos estudios acerca de la relación entre Nog  y su papel en el desarrollo mandibular. Objetivo: Esta revisión hace una descripción de  los factores moleculares que intervienen en la formación de la mandíbula. Se hace un énfasis principalmente en las BMPs, su función, vía de señalización y cómo Nog regula esta vía, para conducir a  formular una  hipótesis del posible papel de este gen en el desarrollo mandibular y cómo su alteración podría llegar a causar el micrognatismo mandibular.