THE PHD FINGER - IMPLICATIONS FOR CHROMATIN-MEDIATED TRANSCRIPTIONAL REGULATION
THE PHD FINGER - IMPLICATIONS FOR CHROMATIN-MEDIATED TRANSCRIPTIONAL REGULATION
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DOI：
10.1016/s0968-0004(00)88957-4
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发表时间：
1995-02-01
影响因子：
13.8
通讯作者：
STEWART, AF
中科院分区：
文献类型：
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作者：
AASLAND, R;GIBSON, TJ;STEWART, AF
在果蝇发育过程中，聚omb和trithorax组基因（Pc-G和trx-G）需要维持群集同源基因fflOM的稳定表达模式。C) 1, 2。几行o！有证据表明，PeG和trx-G通过与染色质相互作用或修饰发挥作用。Polycomb蛋白在异染色质中也有一个结构域（terh,~ d）。混合蛋白，HPI（文献3）。Brahma由trx-G基因编码，与SWI21SNF2具有广泛的相似性（包括一个溴域蛋白4）（参考文献5），SWI21SNF2是酵母中多组分转录激活因子的一部分，似乎可以调节其所调节基因的染色质结构。遗传分析还表明，Pc- g对HOM~连续调控区域的抑制是通过一种机制发生的，这种机制涉及沿基因簇a， 6的异染色质样结构的繁殖。trx蛋白的|的羧基末端部分与另一个成员zeste蛋白的增强子E (z)的羧基末端紧密相连。G，提示Pc-G和trx43基因之间存在功能关系7。trx-G基因作为Pc-G突变体的抑制基因被分离出来，这一事实强调了这种关系。这种染色质介导的转录调控似乎在进化过程中是保守的，因为已经分离出了Pc-G和trx-G的几种脊椎动物同源物。HRX （A/I）就是一个例子。1, M/I)， trx的人类同源物参与急性白血病的染色体易位8,9。利用最近公布的Pc机序列。以G蛋白Polycomblike (Pcl) l作为探针进行序列相似性搜索，我们发现一个类似锌的基序在Pcl中出现2次，在trx和HRX中出现3次（图1）。该基序具有独特的cys4 - his - cys3模式，跨越约50-80个残基。这种保守模式，包括额外的保守位置，与核调节蛋白中出现的两个类似大小的基序明显不同；半胱氨酸。~-His-Cys4 RING linger n和cys2 - hyscyss LIM'domain 1,2, 13（见表1）。
During Drosophila development, the Polyeomb and trithorax group genes (Pc-G and trx-G) are required to maintain stable expression patterns for the clustered homeotlc genes fflOM. C) 1, 2. Several lines o! evidence suggest that PeG and trx-G exert their effects through interaction wlth, or modification of, chromatln. The Polycomb protein has a domain (terh,~ d the chromodomaln) also found in a heterochromatln~. blndlng protein, HPI (Ref. 3). Brahma, encoded by a trx-G gene, has extensive similarity (including a bromodomaln 4) to SWI21SNF2 (Ref. 5), which Is part of a multl-component transcriptional activator In yeast that appears to modulate the chromatln structure of the genes it regulates. Genetic analysis has also suggested that repression by Pc-G of successive regulatory regions of HOM~ occurs by a mechanism Involving propagation of a heterochromatlnqlke structure along the gene cluster a, 6The carboxy-termlnal part o| the trx protein shows shnllarity to the carboxyl terminus of the Enhancer of zeste protein, E (z), another member el the Pc. G, suggesting that there is a functional relationship among the Pc-G and trx43 genes 7. This relationship Is underscored by the fact that trx-G genes are Isolated as suppressors of Pc-G mutants. This type of chromatin-medlated transcriptional regulation appears to be conserved through evolution, since several vertebrate homologues of Pc-G and trx-G have been isolated. One example Is HRX (A/I. 1, M/I), a human homologue of trx involved In chromosomal translocatlons in acute leukaemla 8, 9.Using the recently published sequence of the Pc. G protein Polycomblike (Pcl) l as a probe in sequence similarity searches, we found that a zinc-linger-like motif occurs twice in Pcl and t~ iree times tn trx and HRX (Fig. 1). This motif has a unique Cys4-His-Cys 3 pattern, spanning approximately 50-80 residues. The pattern of conservation, which includes additional conserved positions, is clearly distinct from two similarly sized motifs that also occur in nuclear regulatory proteins; the Cys.~-His-Cys4 RING linger n and the Cys2-HisLCys s LIM'domainl2, 13 (see Table I).