Chromatin modification influences gene expression by either repressing or activating genes, depending on the specific histone mark. Chromatin structure can also influence alternative splicing of transcripts; however, the mechanisms by which epigenetic marks influence splicing are poorly understood. A report in the current issue of the JCI highlights the biological importance of the coordinated control of alternative pre-mRNA splicing by chromatin structure and transcriptional elongation. Yuan et al. found that mutation of the histone methyl transferase SEDT2 affects alternative splicing fates of several key regulatory genes, including those involved in Wnt signaling. As a consequence, loss of SEDT2 in the intestine aggravated Wnt/β-catenin signaling effects, thereby leading to colorectal cancer.

染色质修饰会通过抑制或激活基因来影响基因表达，具体取决于特定的组蛋白标记。染色质结构也可以影响转录物的选择性剪接；然而，表观遗传标记影响剪接的机制了解甚少。JCI当前一期的一份报告着重指出了通过染色质结构和转录延伸来协调控制替代性前mRNA剪接的生物学重要性。袁等人。发现组蛋白甲基转移酶SEDT2的突变会影响几个关键调控基因的替代剪接命运，包括与Wnt信号转导有关的基因。结果，肠中SEDT2的丧失加剧了Wnt /β-catenin信号传导作用，从而导致了结直肠癌。