SWI/SNF-dependent genes are defined by their chromatin landscape.

SWI/SNF complexes are evolutionarily conserved, ATP-dependent chromatin remodeling machines. Here, we characterize the features of SWI/SNF-dependent genes using BRM014, an inhibitor of the ATPase activity of the complexes. We find that SWI/SNF activity is required to maintain chromatin accessibility and nucleosome occupancy for most enhancers but not for most promoters. SWI/SNF activity is needed for expression of genes with low to medium levels of expression that have promoters with (1) low chromatin accessibility, (2) low levels of active histone marks, (3) high H3K4me1/H3K4me3 ratio, (4) low nucleosomal phasing, and (5) enrichment in TATA-box motifs. These promoters are mostly occupied by the canonical Brahma-related gene 1/Brahma-associated factor (BAF) complex. These genes are surrounded by SWI/SNF-dependent enhancers and mainly encode signal transduction, developmental, and cell identity genes (with almost no housekeeping genes). Machine-learning models trained with different chromatin characteristics of promoters and their surrounding regulatory regions indicate that the chromatin landscape is a determinant for establishing SWI/SNF dependency.

Co-transcriptional splicing efficiency is a gene-specific feature that can be regulated by TGFß.

Differential splicing efficiency of specific introns is a mechanism that dramatically increases protein diversity, based on selection of alternative exons for the final mature mRNA. However, it is unclear whether splicing efficiency of introns within the same gene is coordinated and eventually regulated as a mechanism to control mature mRNA levels. Based on nascent chromatin-associated RNA-sequencing data, we now find that co-transcriptional splicing (CTS) efficiency tends to be similar between the different introns of a gene. We establish that two well-differentiated strategies for CTS efficiency exist, at the extremes of a gradient: short genes that produce high levels of pre-mRNA undergo inefficient splicing, while long genes with relatively low levels of pre-mRNA have an efficient splicing. Notably, we observe that genes with efficient CTS display a higher level of mature mRNA relative to their pre-mRNA levels. Further, we show that the TGFß signal transduction pathway regulates the general CTS efficiency, causing changes in mature mRNA levels. Taken together, our data indicate that CTS efficiency is a gene-specific characteristic that can be regulated to control gene expression.