Hematopoietic-specific activators establish an overlapping pattern of histone acetylatin and methylation within a mammalian chromatin domain
Hematopoietic-specific activators establish an overlapping pattern of histone acetylatin and methylation within a mammalian chromatin domain
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DOI：
10.1073/pnas.212389499
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发表时间：
2002-10-29
影响因子：
11.1
通讯作者：
Bresnick, EH
中科院分区：
文献类型：
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作者：
Kiekhaefer, CM;Grass, JA;Bresnick, EH
通过乙酰化、甲基化和磷酸化对组蛋白进行翻译后修饰是调节染色质结构的常见模式，因此也是多种核过程的常见模式。一种这样的修饰，甲基化组蛋白H3在赖氨酸-4（H3-mel 4）与哺乳动物染色质中的超乙酰化组蛋白H3和H4共定位。尽管活化剂直接募集乙酰转移酶，但H3-meK4的建立过程尚不清楚。我们测试了造血特异性激活剂NF-E2和加塔-1是否介导β-珠蛋白基因的反式激活，诱导组蛋白乙酰化和H3-meK4。通过使用NF-E2-和加塔-1-null细胞系，我们发现这两种激活剂在转录激活后诱导启动子H3乙酰化。然而，对H3-mek4的分析揭示了NF-E2和加塔-1在betamajor启动子处差异性地调节染色质修饰。NF-E2而非加塔-1在启动子处诱导H3-meK4。因此，在NF-E2和加塔-1激活内源基因转录至少570倍的条件下，这些激活剂诱导H3-meK 4的能力不同。尽管在上游基因座控制区的超敏位点2处存在强H3-meK4，但在该位点建立H3-meK4不需要任何因子。这些结果支持了一种模型，其中多个组织特异性激活剂共同发挥作用，以组装复合组蛋白修饰模式，由重叠的组蛋白乙酰化和甲基化组成。由于加塔-1在启动子处诱导H3乙酰化，但不诱导H3-meK4，因此可以独立地建立复合组蛋白修饰模式的H3乙酰化和H3-meK4组分。
Posttranslational modification of histones through acetylation, methylation, and phosphorylation is a common mode of regulating chromatin structure and, therefore, diverse nuclear processes. One such modification, methylated histone H3 at lysine-4 (H3-mel4) colocalizes with hyperacetylated histones H3 and H4 in mammalian chromatin. Whereas activators directly recruit acetyltransferases, the process whereby H3-meK4 is established is unknown. We tested whether the hematopoietic-specific activators NF-E2 and GATA-1, which mediate transactivation of the beta-globin genes, induce both histone acetylation and H3-meK4. Through the use of NF-E2- and GATA-1-null cell lines, we show that both activators induce H3 acetylation at the promoter upon transcriptional activation. However, analysis of H3-mek4 revealed that NF-E2 and GATA-1 differentially regulate chromatin modifications at the betamajor promoter. NF-E2, but not GATA-1, induces H3-meK4 at the promoter. Thus, under conditions in which NF-E2 and GATA-1 activate the transcription of an endogenous gene at least 570-fold, these activators differ in their capacity to induce H3-meK4. Despite strong H3-meK4 at hypersensitive site 2 of the upstream locus control region, neither factor was required to establish H3-meK4 at this site. These results support a model in which multiple tissue-specific activators collectively function to assemble a composite histone modification pattern, consisting of overlapping histone acetylation and methylation. As GATA-1 induced H3 acetylation, but not H3-meK4, at the promoter, H3 acetylation and H3-meK4 components of a composite histone modification pattern can be established independently.