The mechanisms that regulate the switch between epidermal progenitor state and differentiation are not fully understood. Recent findings indicate that the chromatin remodelling BAF complex (Brg1-associated factor complex or SWI/SNF complex) and the transcription factor p63 mutually recruit one another to open chromatin during epidermal differentiation. Here, we identify a long non-coding transcript that includes an ultraconserved element, uc.291, which physically interacts with ACTL6A and modulates chromatin remodelling to allow differentiation. Loss of uc.291 expression, both in primary keratinocytes and in three-dimensional skin equivalents, inhibits differentiation as indicated by epidermal differentiation complex genes down-regulation. ChIP experiments reveal that upon uc.291 depletion, ACTL6A is bound to the differentiation gene promoters and inhibits BAF complex targeting to induce terminal differentiation genes. In the presence of uc.291, the ACTL6A inhibitory effect is released, allowing chromatin changes to promote the expression of differentiation genes. Thus, uc.291 interacts with ACTL6A to modulate chromatin remodelling activity, allowing the transcription of late differentiation genes.

中文翻译：

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长链非编码 RNA uc.291 通过干扰 ACTL6A/BAF 复合物来控制上皮分化。

调节表皮祖细胞状态和分化之间转换的机制尚不完全清楚。最近的研究结果表明，染色质重塑 BAF 复合物（Brg1 相关因子复合物或 SWI/SNF 复合物）和转录因子 p63 在表皮分化过程中相互招募以打开染色质。在这里，我们确定了一个长的非编码转录本，其中包括一个超保守元件 uc.291，它与 ACTL6A 物理相互作用并调节染色质重塑以允许分化。原代角质形成细胞和三维皮肤等效物中 uc.291 表达的丧失抑制了分化，如表皮分化复合基因下调所示。ChIP 实验表明，在 uc.291 耗尽后，ACTL6A 与分化基因启动子结合，抑制 BAF 复合物靶向诱导终末分化基因。在uc.291存在的情况下，释放ACTL6A抑制作用，使染色质发生变化，促进分化基因的表达。因此，uc.291 与 ACTL6A 相互作用以调节染色质重塑活性，从而允许晚期分化基因的转录。