Sequence organization and matrix attachment regions of the human serine protease inhibitor gene cluster at 14q32.1

Sequence organization and matrix attachment regions of the human serine protease inhibitor gene cluster at 14q32.1
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DOI:
10.1007/s00335-003-2311-y
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发表时间:
2004-03-01
期刊:
影响因子:
2.5
通讯作者:
Fournier, REK
Fournier, REK
中科院分区:
生物学4区
文献类型:
--
作者:
Namciu, SJ;Friedman, RD;Fournier, REK

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位于 14q32.1 的人类丝氨酸蛋白酶抑制剂 (serpin) 基因簇是研究基因活性和染色质结构调控的有用模型系统。我们之前证明了该区域的 6 个已知的丝氨酸蛋白酶抑制剂基因被组织成两个亚簇,每个亚簇由三个基因组成,每个亚簇占据大约 370 kb 的 DNA。为了更全面地了解该区域的基因组组织,我们根据 Genscope 测序联盟 (http://www.genscope.cns.fr/) 的数据注释了 1 Mb 序列重叠群。我们报告了 14q32.1 簇内存在 11 个不同的丝氨酸蛋白酶抑制蛋白基因,包括两个新的 α1-抗蛋白酶样基因序列、一个卡利司他汀样序列和两个最近鉴定的丝氨酸蛋白酶抑制蛋白(之前未映射到 14q32.1)。丝氨酸蛋白酶抑制剂簇近端和远端的基因组区域包含多种具有不同功能的不相关基因序列。为了深入了解该区域的染色质组织,使用 MAR-Wiz 算法鉴定了具有假定核基质结合潜力的序列,并在体外测试了这些 MAR-Wiz 候选序列的核基质结合活性。观察到 MAR-Wiz 预测与生化测试结果之间存在一些差异。讨论了丝氨酸蛋白酶抑制剂基因簇的基因组组织。
The human serine protease inhibitor (serpin) gene cluster at 14q32.1 is a useful model system for studying the regulation of gene activity and chromatin structure. We demonstrated previously that the six known serpin genes in this region were organized into two subclusters of three genes each that occupied similar to370 kb of DNA. To more fully understand the genomic organization of this region, we annotated a 1-Mb sequence contig from data from the Genoscope sequencing consortium (http:// www.genoscope.cns.fr/). We report that 11 different serpin genes reside within the 14q32.1 cluster, including two novel alpha1-antiproteinase-like gene sequences, a kallistatin-like sequence, and two recently identified serpins that had not been mapped previously to 14q32.1. The genomic regions proximal and distal to the serpin cluster contain a variety of unrelated gene sequences of diverse function. To gain insight into the chromatin organization of the region, sequences with putative nuclear matrix-binding potential were identified by using the MAR-Wiz algorithm, and these MAR-Wiz candidate sequences were tested for nuclear matrix-binding activity in vitro. Several differences between the MAR-Wiz predictions and the results of biochemical tests were observed. The genomic organization of the serpin gene cluster is discussed.