Graphical Abstract Highlights d SUMO acts on chromatin to maintain cellular identity d SUMO impairs somatic enhancer inactivation early during iPSC reprogramming d Loss of SUMO converts ESCs into a 2C-like state by releasing PRC1.6 from the Dux locus d Loss of SUMO in ESCs leads to genome-wide loss of H3K9me3-dependent heterochromatin

Although heterochromatin is enriched with repressive traits, it is also actively transcribed, giving rise to large amounts of noncoding RNAs. Although these RNAs are responsible for the formation and maintenance of heterochromatin, little is known about how their transcription is regulated. Here, we show that the Snail1 transcription factor represses mouse pericentromeric transcription, acting through the H3K4 deaminase LOXL2. Since Snail1 plays a key role in the epithelial-to-mesenchymal transition (EMT), we analyzed the regulation of heterochromatin transcription in this process. At the onset of EMT, one of the major structural heterochromatin proteins, HP1α, is transiently released from heterochromatin foci in a Snail1/LOXL2-dependent manner, concomitantly with a downregulation of major satellite transcription. Moreover, preventing the downregulation of major satellite transcripts compromised the migratory and invasive behavior of mesenchymal cells. We propose that Snail1 regulates heterochromatin transcription through LOXL2, thus creating the favorable transcriptional state necessary for completing EMT.

Lamins (A/C and B) are major constituents of the nuclear lamina (NL). Structurally conserved lamina-associated domains (LADs) are formed by genomic regions that contact the NL. Lamins are also found in the nucleoplasm, with a yet unknown function. Here we map the genome-wide localization of lamin B1 in an euchromatin-enriched fraction of the mouse genome and follow its dynamics during the epithelial-to-mesenchymal transition (EMT). Lamin B1 associates with actively expressed and open euchromatin regions, forming dynamic euchromatin lamin B1-associated domains (eLADs) of about 0.3 Mb. Hi-C data link eLADs to the 3D organization of the mouse genome during EMT and correlate lamin B1 enrichment at topologically associating domain (TAD) borders with increased border strength. Having reduced levels of lamin B1 alters the EMT transcriptional signature and compromises the acquisition of mesenchymal traits. Thus, during EMT, the process of genome reorganization in mouse involves dynamic changes in eLADs.

The GEO accession number for the data referred to this paper is GSE35600.

The lysyl oxidase (LOX) family of proteins (LOX and LOXL1-LOXL4) oxidize amino groups located in the e-position in lysines to generate an aldehyde group. In general, they are considered as extracellular proteins and have elastin and collagen as their main substrates. However, recent findings suggest a critical intracellular role for LOX and LOXL2 in transcriptional regulation. In this review, we highlight what is known about the transcriptional role of these two members of the family. Intriguingly, both the intracellular localization of these proteins and the fact that histones have been revealed to be their substrates place this family of proteins within the epigenetic field.