Intergenic Transcription, Cell-Cycle and the Developmentally Regulated Epigenetic Profile of the Human Beta-Globin Locus

Several lines of evidence have established strong links between transcriptional activity and specific post-translation modifications of histones. Here we show using RNA FISH that in erythroid cells, intergenic transcription in the human β-globin locus occurs over a region of greater than 250 kb including several genes in the nearby olfactory receptor gene cluster. This entire region is transcribed during S phase of the cell cycle. However, within this region there are ∼20 kb sub-domains of high intergenic transcription that occurs outside of S phase. These sub-domains are developmentally regulated and enriched with high levels of active modifications primarily to histone H3. The sub-domains correspond to the β-globin locus control region, which is active at all developmental stages in erythroid cells, and the region flanking the developmentally regulated, active globin genes. These results correlate high levels of non-S phase intergenic transcription with domain-wide active histone modifications to histone H3

A 220-nucleotide deletion of the intronic enhancer reveals an epigenetic hierarchy in immunoglobulin heavy chain locus activation

A tissue-specific transcriptional enhancer, Eμ, has been implicated in developmentally regulated recombination and transcription of the immunoglobulin heavy chain (IgH) gene locus. We demonstrate that deleting 220 nucleotides that constitute the core Eμ results in partially active locus, characterized by reduced histone acetylation, chromatin remodeling, transcription, and recombination, whereas other hallmarks of tissue-specific locus activation, such as loss of H3K9 dimethylation or gain of H3K4 dimethylation, are less affected. These observations define Eμ-independent and Eμ-dependent phases of locus activation that reveal an unappreciated epigenetic hierarchy in tissue-specific gene expression

Single-Nucleosome Mapping of Histone Modifications in S. cerevisiae

Covalent modification of histone proteins plays a role in virtually every process on eukaryotic DNA, from transcription to DNA repair. Many different residues can be covalently modified, and it has been suggested that these modifications occur in a great number of independent, meaningful combinations. Published low-resolution microarray studies on the combinatorial complexity of histone modification patterns suffer from confounding effects caused by the averaging of modification levels over multiple nucleosomes. To overcome this problem, we used a high-resolution tiled microarray with single-nucleosome resolution to investigate the occurrence of combinations of 12 histone modifications on thousands of nucleosomes in actively growing S. cerevisiae. We found that histone modifications do not occur independently; there are roughly two groups of co-occurring modifications. One group of lysine acetylations shows a sharply defined domain of two hypo-acetylated nucleosomes, adjacent to the transcriptional start site, whose occurrence does not correlate with transcription levels. The other group consists of modifications occurring in gradients through the coding regions of genes in a pattern associated with transcription. We found no evidence for a deterministic code of many discrete states, but instead we saw blended, continuous patterns that distinguish nucleosomes at one location (e.g., promoter nucleosomes) from those at another location (e.g., over the 3′ ends of coding regions). These results are consistent with the idea of a simple, redundant histone code, in which multiple modifications share the same role

Transcription and Chromatin Organization of a Housekeeping Gene Cluster Containing an Integrated β-Globin Locus Control Region

The activity of locus control regions (LCR) has been correlated with chromatin decondensation, spreading of active chromatin marks, locus repositioning away from its chromosome territory (CT), increased association with transcription factories, and long-range interactions via chromatin looping. To investigate the relative importance of these events in the regulation of gene expression, we targeted the human β-globin LCR in two opposite orientations to a gene-dense region in the mouse genome containing mostly housekeeping genes. We found that each oppositely oriented LCR influenced gene expression on both sides of the integration site and over a maximum distance of 150 kilobases. A subset of genes was transcriptionally enhanced, some of which in an LCR orientation-dependent manner. The locus resides mostly at the edge of its CT and integration of the LCR in either orientation caused a more frequent positioning of the locus away from its CT. Locus association with transcription factories increased moderately, both for loci at the edge and outside of the CT. These results show that nuclear repositioning is not sufficient to increase transcription of any given gene in this region. We identified long-range interactions between the LCR and two upregulated genes and propose that LCR-gene contacts via chromatin looping determine which genes are transcriptionally enhanced

Chapitre III. La conception culturaliste de l’éco-développement

Protection de l’environnement naturel, réorganisation volontariste de l’économie spatiale et satisfaction des besoins humains fondamentaux, tout cela fait certainement partie de l’idée d’écodéveloppement. Dans la forme que ces objectifs ont revêtu dans l’approche conventionnelle, ils diffèrent de façon marquante des principes présentés par Cunha, Greer-Wootten et Racine. Nous pensons que cette différence tient à la conception spécifique de la société et de la nature qui distingue l’approche c..

Chapitre II. L’origine de l’éco-développement dans l’approche conventionnelle

1. Présupposés de base En ce qui concerne les problèmes du développement, l’approche conventionnelle est dominée par la théorie économique néo-classique. Ici l’environnement naturel est représenté sous la forme de ressources qui acquièrent une valeur en tant que facteurs de production. La plupart des ressources sont également dotées d’une caractéristique intrinsèque, celle de leur localisation qui détermine une variable d’accessibilité par rapport à tous les autres lieux. En général, dans cet..

Chapitre I. La société et la nature

« Les géographes se contentent de juxtaposer (des faits) alors même que la question fondamentale de leur discipline — comment les conditions écologiques agissent sur les formations sociales — reste à peu près sans réponse ». Que ce jugement formulé il y a déjà huit ans par Samir Amin soit justifié ou non, l’article de Cunha, Greer-Wooten et Racine prouve au moins que le problème de fond qu’il soulevait alors est toujours à l’ordre du jour et que les travaux géographiques récents consistent en..

Terrains vagues et terres promises

Le voisinage n’est pas nécessairement le garant d’une bonne connaissance mutuelle. Et ce qui vaut pour les hommes peut s’appliquer aussi aux disciplines scientifiques. Les « études du développement » ne font en effet que de rares emprunts explicites aux travaux des géographes, comme si la longue appartenance de ceux-ci à la tradition académique devait nécessairement priver leur démarche d’une réelle pertinence pour les problèmes urgents du monde contemporain. Ce Cahiers donne la parole aux géographes pour tenter de saisir aussi bien la spécificité de leur perspective que le débat dont elle fait l’objet… Au moment où les études du développement s’occupent d’environnement et d’écologie, elles ne peuvent négliger l’apport de la géographie qui a fait de ce facteur un de ses thèmes de réflexion..