草菇基因组中11个漆酶同源基因的生物信息学分析及铜离子对其表达的影响

通过分析草菇基因组中11个漆酶同源基因所编码的蛋白的性质、转录调控元件和测定铜离子存在条件下的草菇漆酶活性及11个漆酶基因的转录水平,揭示了草菇漆酶基因的各自特性、差异以及基因功能与进化机制。分析表明,这11个漆酶同源基因编码的蛋白具有508–562aa个氨基酸,分子量和理论等电点分别为56.25–60.75kDa和4.51–6.18（未经翻译后修饰）,且都具有真菌漆酶铜离子结合区域的特征序列、4个能够结合催化底物的环形结构以及信号肽序列,都属于分泌性的胞外蛋白,但其底物结合位点数目、loop序列的一致性、跨膜区域数目和位置以及信号肽位置等存在较大差异。草菇11个漆酶起始密码子上游2 000bp的序列中含有真核生物的基本转录调控元件（TATA-box,CAAT-box及GC-box）和多个潜在的调控元件（MRE、XRE、STRE、HSE、ARE、TRE、NIT元件等）,但每个基因所含调控元件数目及种类各有不同。在液体培养条件下,铜离子能够诱导除vv-lac2、vv-lac3和vv-lac7之外的其余8个草菇漆酶基因的表达,且适宜浓度的铜离子有助于草菇漆酶活性的增加。     

Long-distance control of origin choice and replication timing in the human beta-globin locus are independent of the locus control region

DNA replication in the human beta-globin locus is subject to long-distance regulation. In murine and human erythroid cells, the human locus replicates in early S phase from a bidirectional origin located near the beta-globin gene. This Hispanic thalassemia deletion removes regulatory sequences located over 52 kb from the origin, resulting in replication of the locus from a different origin, a shift in replication timing to late S phase, adoption of a closed chromatin conformation, and silencing of globin gene expression in murine erythroid cells. The sequences deleted include nuclease-hypersensitive sites 2 to 5 (5'HS2-5) of the locus control region (LCR) plus an additional 27-kb upstream region. We tested a targeted deletion of 5'HS2-5 in the normal chromosomal context of the human beta-globin locus to determine the role of these elements in replication origin choice and replication timing. We demonstrate that the 5'HS2-5-deleted locus initiates replication at the appropriate origin and with normal timing in murine erythroid cells, and therefore we conclude that 5'HS2-5 in the classically defined LCR do not control replication in the human beta-globin locus. Recent studies also show that targeted deletion of 5'HS2-5 results in a locus that lacks globin gene expression yet retains an open chromatin conformation. Thus, the replication timing of the locus is closely correlated with nuclease sensitivity but not globin gene expression.     

基因非编码区与转录调控元件的识别研究

随着后基因组时代的到来,非编码区的研究已经成为科学家面临的挑战,对基因非编码区的一个主要研究方向就是对调控元件的研究。识别转录调控元件是理解基因转录机制和表达模式的关键。较全面地介绍了基因非编码区以及调控元件,包括功能和作用,常用识别算法,并对常用数据库进行介绍,提出可能的研究方法和发展方向。