Suppression of pervasive noncoding transcription in embryonic stem cells by esBAF.
Suppression of pervasive noncoding transcription in embryonic stem cells by esBAF.
复制标题
DOI：
10.1101/gad.253534.114
复制
发表时间：
2015-02-15
影响因子：
10.5
通讯作者：
Fazzio TG
中科院分区：
文献类型：
--
作者：
Hainer SJ;Gu W;Carone BR;Landry BD;Rando OJ;Mello CC;Fazzio TG
Hainer等人表明，esBAF（SWI/SNF家族核小体重塑因子）抑制小鼠胚胎干细胞基因组中约57，000个核小体缺失区（NDRs）的非编码RNA（ncRNA）转录。esBAF的功能，以加强邻近NDRs的核小体占用，但不是其功能，以维持NDRs在核小体-游离状态，是必要的沉默转录超过ncDNA。最后，强定位的核小体抑制ncRNA的能力取决于其翻译定位。大约75%的人类基因组被转录，其中大部分不编码蛋白质。然而，许多非编码RNA（ncRNA）在转录后迅速降解，并且相对较少具有既定功能，质疑这一观察结果的意义。在这里，我们表明esBAF，一个SWI/SNF家族核小体重塑因子，抑制小鼠胚胎干细胞（ESC）基因组中约57，000个核小体缺失区（NDRs）的ncRNA转录。我们表明，esBAF的功能，既保持NDRs核小体自由，并促进NDRs附近的核小体占有率升高。esBAF耗尽后相邻核小体占据率的降低与ncRNA表达强烈相关，表明侧翼核小体形成了普遍转录的屏障。在使用核小体定位序列迫使核小体占据两个NDRs附近后，我们发现esBAF不再需要沉默转录。因此，esBAF的功能，以加强邻近NDRs的核小体占用，而不是其功能，以保持NDRs在核小体游离状态，是必要的沉默转录超过ncDNA。最后，我们表明，一个强定位的核小体抑制ncRNA的能力取决于其翻译定位。这些数据揭示了esBAF在抑制ESC中开放染色质区域的普遍转录中的新作用。
Hainer et al. show that esBAF, a SWI/SNF family nucleosome remodeling factor, suppresses transcription of noncoding RNAs (ncRNAs) from ∼57,000 nucleosome-depleted regions (NDRs) throughout the genome of mouse embryonic stem cells. esBAF’s function to enforce nucleosome occupancy adjacent to NDRs, but not its function to maintain NDRs in a nucleosome-free state, is necessary for silencing transcription over ncDNA. Finally, the ability of a strongly positioned nucleosome to repress ncRNA depends on its translational positioning. Approximately 75% of the human genome is transcribed, the majority of which does not encode protein. However, many noncoding RNAs (ncRNAs) are rapidly degraded after transcription, and relatively few have established functions, questioning the significance of this observation. Here we show that esBAF, a SWI/SNF family nucleosome remodeling factor, suppresses transcription of ncRNAs from ∼57,000 nucleosome-depleted regions (NDRs) throughout the genome of mouse embryonic stem cells (ESCs). We show that esBAF functions to both keep NDRs nucleosome-free and promote elevated nucleosome occupancy adjacent to NDRs. Reduction of adjacent nucleosome occupancy upon esBAF depletion is strongly correlated with ncRNA expression, suggesting that flanking nucleosomes form a barrier to pervasive transcription. Upon forcing nucleosome occupancy near two NDRs using a nucleosome-positioning sequence, we found that esBAF is no longer required to silence transcription. Therefore, esBAF’s function to enforce nucleosome occupancy adjacent to NDRs, and not its function to maintain NDRs in a nucleosome-free state, is necessary for silencing transcription over ncDNA. Finally, we show that the ability of a strongly positioned nucleosome to repress ncRNA depends on its translational positioning. These data reveal a novel role for esBAF in suppressing pervasive transcription from open chromatin regions in ESCs.
登录
查看更多内容
影响因子：
11.4
作者：
ALMER, A;HORZ, W
通讯作者：
HORZ, W
影响因子：
14.9
作者：
Castelnuovo, Manuele;Zaugg, Judith B.;Stutz, Francoise
通讯作者：
Stutz, Francoise
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
64.5
作者：
Carrozza, MJ;Li, B;Workman, JL
通讯作者：
Workman, JL
影响因子：
9.8
作者：
Cheung V;Chua G;Batada NN;Landry CR;Michnick SW;Hughes TR;Winston F
通讯作者：
Winston F