Chromatin dynamics underlying cellular memory

通过本研究，我们取得了以下研究成果。结论1.GAGA因子-事实复合体招募染色质重塑复合体PBAP到Pc/Trx反应元件，诱导染色质重塑，维持HOX基因的表达。GagA因子-事实复合体与白色基因下游的GA重复序列结合，诱导染色质重塑，用其变异体H3.3取代组蛋白H3，并通过抵消异染色质的扩散来维持白色基因的表达。非编码RNA通过Pc/Trx反应元件转录调控HOX基因的表达。超卷曲因子被MOF补充到组蛋白H4 K16上的染色质乙酰化，并通过与ISWI的相互作用参与X染色体的剂量补偿。Ash1基因敲除小鼠是纯合子存活的，但表现出背部基因的同源转化。SPT16基因敲除小鼠在纯合子中是胚胎致死的。它的杂合子表现出免疫球蛋白亚类水平的偏差。

We have obtained following results through this study.1. GAGA factor FACT complex recruits chromatin remodeling complex PBAP to Pc/trx response elements, induces chromatin remodeling, and maintains expression of Hox genes.2. GAGA factor-FACT complex binds to a GA repeat sequence downstream the white gene, induces chromatin remodeling, replaces histone H3 by its variant H3.3, and maintains white gene expression by counteracting the heterochromatin spreading.3. Transcription of non-coding RNA through Pc/trx response element regulates Hox gene expression.4. Supercoiling factor is recruited to chromatin acetylated at histone H4 K16 by MOF, and contributes dosage compensation of X chromosome through counteracting with ISWI.5. Ash1 knock-out mice are homozygous viable but show homeotic transformation of the back-one. SPT16 knock-out mice are embryonic lethal in homozygotes. Its heterozygotes show a deviation in the levels of IgG sublasses.