Gene specific signatures by H3K4me2 and H3K27me3 modifications during retina maturation

Control of neural organogenesis is a complex process and the epigenetic contribution is largely unknown. Here we have followed the genome-wide distribution of two important histone H3 modifications, H3K4me2 and H3K27me3 during late mouse retina development. We found that genes expressed only in mature rod photoreceptors, have a unique signature consisting of de-novo accumulation of H3K4me2 both at the transcription start site (TSS) and over the whole gene that correlates with the increase in transcription, but no accumulation of H3K27me3 at any stage. We also found that distribution of H3K4me2 and H3K27me3 on the genes widely expressed is not always associated with their transcriptional levels. Genes without H3K4me2 and H3K27me3 accumulation at any stage represent a group of transcripts never expressed in retina. The epigenetic signatures defined by H3K4me2 and H3K27me3 can distinguish cell-type specific genes from widespread transcripts and may be reflective of cell specificity during retina maturation. Examination of 2 different histone modifications during late mouse retina development.

神经器官发生的调控是一个复杂过程，其表观遗传贡献在很大程度上仍未明确。本研究追踪了小鼠视网膜发育后期两种重要的组蛋白H3修饰——H3K4me2与H3K27me3的全基因组分布情况。我们发现，仅在成熟杆状光感受器细胞中表达的基因具有独特的表观遗传特征：即在转录起始位点（Transcription Start Site, TSS）及整个基因区域内出现H3K4me2的从头积累，这一现象与转录水平的升高相关，但在任一发育阶段均未出现H3K27me3的积累。我们还发现，在广泛表达的基因上，H3K4me2与H3K27me3的分布并不总是与其转录水平相关联。在所有发育阶段均未检测到H3K4me2和H3K27me3积累的基因，代表了一类从未在视网膜中表达的转录本。由H3K4me2和H3K27me3所定义的表观遗传特征，能够区分细胞类型特异性基因与广泛表达的转录本，或可反映视网膜成熟过程中的细胞特异性。本研究针对小鼠视网膜发育后期的两种不同组蛋白修饰展开了分析。