A peculiar mutation in the DNA-binding/dimerization domain of NFIX causes Sotos-like overgrowth syndrome: A new case

The Nuclear Factor I-X (NFIX) is a member of the nuclear factor I (NFI) family proteins, which are implicated as site-specific DNA-binding proteins and is deleted or mutated in a subset of patients with Sotos-like overgrowth syndrome and in patients with Marshall–Smith syndrome. We evaluated an additional patient with clinical features of Sotos-like syndrome by sequencing analysis of the NFIX gene and identified a 21 nucleotide in frame deletion predicting loss of 7 amino acids in the DNA-binding/dimerization domain of the NFIX protein. The deleted residues are all evolutionally conserved amino acids. The present report further confirms that mutations in DNA-binding/dimerization domain cause haploinsufficiency of the NFIX protein and strongly suggests that in individuals with Sotos-like features unrelated to NSD1 changes genetic testing of NFIX should be considered.     

昆虫小器官RNA荧光原位杂交技术

【目的】在昆虫基因表达和功能研究中,RNA原位杂交技术越来越受到青睐。该技术不仅能定性定量反应基因表达的时空特异性,而且能在细胞水平上检测基因表达的调控模式。为了将该技术更好地在昆虫小器官研究中运用,我们以果蝇幼虫翅芽为例优化了改技术。【方法】解剖果蝇3龄幼虫翅芽进行原位杂交实验。【结果】我们发现影响原位杂交结果的因素十分复杂,包括取材时期,探针的合成,预杂交/杂交的时间和温度,清洗时间,适当的对照等。通过RNA荧光原位杂交实验,我们揭示了调控细胞记忆的trithorax基因在3龄翅芽广泛表达,并且受到转录因子Optomotor-blind的负调控。【结论】这一技术方法为研究昆虫小器官的基因表达和调控提供了便捷手段。     

Polycomb homologs are involved in teratogenicity of valproic acid in mice

BACKGROUND: Valproic acid (VPA) is widely used to treat epilepsy and bipolar disorder and is also a potent teratogen, but its teratogenic mechanisms are unknown. We have attempted to describe a fundamental role of the Polycomb group (Pc-G) in VPA-induced transformations of the axial skeleton. METHODS: Pregnant NMRI mice were given a single subcutaneous injection of vehicle or VPA (800 mg/kg) on gestation day (GD) 8. The expression of genes encoding Polycomb and trithorax groups was measured by quantitative real-time RT-PCR using total RNA isolated from the embryos exposed to vehicle or VPA for 1, 3, and 6 hr. In addition, the use of two less teratogenic antiepileptic chemicals valpromide (VPD) and valnoctamide (VCD) provide reliable evidence to support the relationship between VPA teratogenicity and the Polycomb group. RESULTS: At a teratogenic level, VPA inhibits the expression of the Polycomb group genes, including Eed, Ezh2, Zfp144, Bmi1, Cbx2, Rnf2, and YY1 in the mouse embryos. In contrast, neither VPD nor VCD have significant effects on the expression of those genes affected by VPA. The trithorax group (trx-G) gene MLL, which is known to be required to maintain homeobox gene expression such as the Polycomb gene, is not affected by a teratogenic dose of VPA. CONCLUSIONS: We propose that, during embryonic development, VPA may affect the gene silencing pathway mediated by the Polycomb group complex. The epigenetic mechanism of VPA teratogenicity on anteroposterior patterning is suspected.     

Cell context in the control of self-renewal and proliferation regulated by MLL1

Mixed lineage leukemia 1 (MLL1) is a gene that is disrupted by chromosomal translocation characteristically in a large proportion of infant leukemia and also in a fraction of childhood and adult leukemia. MLL1 encodes a chromatin regulatory protein related to the Drosophila Trithorax protein, a well-studied epigenetic factor that functions during development to maintain expression of its target genes. Although tremendous progress has been made understanding the downstream targets of MLL1 fusion oncoproteins and how manipulation of those targets impacts leukemogenesis, very little is known regarding how the initial expression of an MLL1 fusion protein impacts on that cell’s behavior, particularly how the cell cycle is affected. Here, we focused on the function of endogenous MLL1 in the stem and progenitor cell types that are likely to be transformed upon MLL1 translocation. Our studies reveal a differential response of stem or progenitor populations to acute loss of MLL1 on proliferation and survival. These data suggest that the effects of MLL1 fusion oncoproteins will initiate the leukemogenic process differentially depending on the differentiation state of the cell type in which the translocation occurs.     

Chromatin‐based mechanisms of temperature memory in plants

For successful growth and development, plants constantly have to gauge their environment. Plants are capable to monitor their current environmental conditions, and they are also able to integrate environmental conditions over time and store the information induced by the cues. In a developmental context, such an environmental memory is used to align developmental transitions with favourable environmental conditions. One temperature‐related example of this is the transition to flowering after experiencing winter conditions, that is, vernalization. In the context of adaptation to stress, such an environmental memory is used to improve stress adaptation even when the stress cues are intermittent. A somatic stress memory has now been described for various stresses, including extreme temperatures, drought, and pathogen infection. At the molecular level, such a memory of the environment is often mediated by epigenetic and chromatin modifications. Histone modifications in particular play an important role. In this review, we will discuss and compare different types of temperature memory and the histone modifications, as well as the reader, writer, and eraser proteins involved.