Synthesis of ribosomal RNAs (rRNAs) is the major transcriptional event in proliferating cells. In eukaryotes, ribosomal DNA (rDNA) is transcribed by RNA polymerase I from a multicopy locus coexisting in at least two different chromatin states. This heterogeneity of rDNA chromatin has been an obstacle to defining its molecular composition. We developed an approach to analyze differential protein association with each of the two rDNA chromatin states in vivo in the yeast Saccharomyces cerevisiae. We demonstrate that actively transcribed rRNA genes are largely devoid of histone molecules, but instead associate with the high-mobility group protein Hmo1.[Keywords: Chromatin; transcription; ribosomal DNA] Supplemental material is available at http://www.genesdev.org. Received December 11, 2007; revised version accepted February 29, 2008. In the yeast Saccharomyces cerevisiae (hereafter called yeast), >60% of total cellular transcripts are produced from the ribosomal DNA (rDNA) locus by a specific multiprotein enzyme, RNA Polymerase I (Pol I), and an assorted set of additional transcription factors (Reeder 1999;Moss and Stefanovsky 2002;Russell and Zomerdijk 2006). The basal Pol I transcription machinery has been largely defined and consists of two multiprotein complexes, the upstream activating factor (UAF) , and the core factor (CF) (Keys et al. 1994), as well as the TATA-box-binding protein (TBP) (Steffan et al. 1996).The template of RNA Pol I transcription, the yeast ribosomal RNA (rRNA) genes are located on the right arm of chromosome XII in a tandem array of 150-200 copies (Fig. 1), representing almost 10% of the yeast genome. Each of the repeats contains the Pol I-transcribed 35S rRNA gene (precusor of the 5.8S, 18S, and 25S rRNAs) and the RNA Polymerase III (Pol III)-transcribed 5S rRNA gene (Fig. 1). Three different regulatory DNA elements have been identified within the 35S rRNA gene sequence, two of which are located at the 5Ј end of the 35S rDNA, spanning only ∼170 base pairs (bp) (Musters et al. 1989;Kulkens et al. 1991): the upstream element (UE), which is the binding site for the UAF; and the core promoter (CP), where CF can be recruited (Fig. 1). The third element, called the enhancer (ENH), is located at the 3Ј end of the 35S transcription unit (Fig. 1) and was originally identified as exhibiting a stimulatory effect on Pol I transcription in experiments using episomal reporter systems Warner 1984, 1986). However, this sequence has been shown subsequently to be dispensable for RNA Pol I transcription in the chromosomal context (Wai et al. 2001).In each cell, Pol I-transcribed rDNA coexists in two different chromatin states (Conconi et al. 1989). In these studies, cells were treated with the DNA cross-linking drug psoralen, and it was shown that actively transcribed and transcriptionally inactive rRNA genes differed substantially in their degree of psoralen incorporation. The different migration behavior of the corresponding restriction fragments in agarose gel electrophoresis led to the terms s-ban...

The generation of new neurons in the adult brain is modulated by complex stimuli and a broad range of extrinsic signals. It remains a mystery how stem cells and their progeny integrate this wealth of regulatory input to generate a precise number of neurons that matches the physiological needs of the olfactory and hippocampal network. cAMP response element binding protein (CREB)-dependent signalling is controlling essential developmental steps in adult neurogenesis, i.e. survival, maturation and integration of new neurons. Here, we summarize the current knowledge on the function of CREB in adult neurogenesis and discuss the potential of CREB to integrate complex stimuli and to translate these into precise developmental processes in adult neurogenesis. The complex modulation of CREB-signalling may allow the adult neurogenic system to respond to stimuli in a fine-tuned rather than in an on-off fashion.

Neural stem cells (NSCs) generate new hippocampal dentate granule neurons throughout adulthood. The genetic programs controlling neuronal differentiation of adult NSCs are only poorly understood. Here we show that, in the adult mouse hippocampus, expression of the SoxC transcription factors Sox4 and Sox11 is initiated around the time of neuronal commitment of adult NSCs and is maintained in immature neurons. Overexpression of Sox4 and Sox11 strongly promotes in vitro neurogenesis from adult NSCs, whereas ablation of Sox4/Sox11 prevents in vitro and in vivo neurogenesis from adult NSCs. Moreover, we demonstrate that SoxC transcription factors target the promoters of genes that are induced on neuronal differentiation of adult NSCs. Finally, we show that reprogramming of astroglia into neurons is dependent on the presence of SoxC factors. These data identify SoxC proteins as essential contributors to the genetic network controlling neuronal differentiation in adult neurogenesis and neuronal reprogramming of somatic cells.

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