University Brest, Inserm, EFS, UMR 1078, GGB, F-29200 Brest, France.
Laboratoire de Génétique Moléculaire et d'Histocompatibilité, CHRU Brest, UMR 1078, F-29200 Brest, France.
Int J Mol Sci. 2022 Jun 23;23(13):6964. doi: 10.3390/ijms23136964.
The human genome is covered by 8% of candidate -regulatory elements. The identification of distal acting regulatory elements and an understanding of their action are crucial to determining their key role in gene expression. Disruptions of such regulatory elements and/or chromatin conformation are likely to play a critical role in human genetic diseases. Non-syndromic hearing loss (i.e., ) is mostly due to () variations and large deletions. Although several -regulatory elements (CREs) have been described, gene regulation remains not well understood. We investigated the endogenous effect of these CREs with CRISPR (clustered regularly interspaced short palindromic repeats) disruptions and observed expression. To decipher the regulatory landscape, we used the 4C-seq technique and defined new chromatin contacts inside the locus, which permit DNA loops and long-range regulation. Moreover, through ChIP-PCR, we determined the involvement of the MEIS1 transcription factor in expression. Taken together, the results of our study enable us to describe the 3D regulatory landscape.
人类基因组有 8%被认为是调控元件。对远距离作用的调控元件的鉴定及其功能的理解，对于确定它们在基因表达中的关键作用至关重要。这些调控元件和/或染色质构象的破坏很可能在人类遗传疾病中发挥关键作用。非综合征性听力损失（即）主要是由于（）变异和大片段缺失引起的。尽管已经描述了几个 - 调控元件（CREs），但基因调控仍未得到很好的理解。我们用 CRISPR（成簇的、规律间隔的短回文重复序列）干扰这些 CREs，观察到了表达。为了解读的调控景观，我们使用了 4C-seq 技术，在 基因座内定义了新的染色质接触，这允许 DNA 环和长距离调控。此外，通过 ChIP-PCR，我们确定了 MEIS1 转录因子在 表达中的参与。总之，我们的研究结果使我们能够描述的 3D 调控景观。
