Subnuclear segregation of genes and core promoter factors in myogenesis

Abstract

Recent findings implicate alternate core promoter recognition complexes in regulating cellular differentiation. Here we report a spatial segregation of the alternative core factor TAF3, but not canonical TFIID subunits, away from the nuclear periphery, where the key myogenic gene MyoD is preferentially localized in myoblasts. This segregation is correlated with the differential occupancy of TAF3 versus TFIID at the MyoD promoter. Loss of this segregation by modulating either the intranuclear location of the MyoD gene or TAF3 protein leads to altered TAF3 occupancy at the MyoD promoter. Intriguingly, in differentiated myotubes, the MyoD gene is repositioned to the nuclear interior, where TAF3 resides. The specific high-affinity recognition of H3K4Me3 by the TAF3 PHD (plant homeodomain) finger appears to be required for the sequestration of TAF3 to the nuclear interior. We suggest that intranuclear sequestration of core transcription components and their target genes provides an additional mechanism for promoter selectivity during differentiation.

Olfactory receptor genes expressed in distinct lineages are sequestered in different nuclear compartments

“…For example, during erythroid differentiation, the β-globin locus moves away from the periphery, where it associates with corepressors, into a euchromatic nuclear compartment that contains a transcriptional activator essential for its expression (40). During myogenesis, the relocation of MyoD away from the nuclear periphery is accompanied by a switch in core factors from TFIID to the alternate, and exclusively nucleoplasmic, TAF3 (41). It is conceivable that such mechanisms regulate the expression of numerous genes, including Taar and Olfr genes.…”

Topologically associated domains enriched for lineage-specific genes reveal expression-dependent nuclear topologies during myogenesis

“…To control for levels of gene expression, NE-TAD 2 serves a double purpose as it encodes the most highly induced gene (CASQ2) found on HSA1 during myogenesis, but no other differentially expressed genes. In comparison, LE-TAD 7 contains both the MYOG (Myogenin) gene locus, which was previously implicated in repositioning during myogenesis (10,11), and a significant number of myogenic-restricted genes (SI Appendix, Table S2). …”

“…The combination of genomic sequences and genome-wide expression studies have revealed another form of nonrandom gene distribution, termed tandem gene arrays (TGAs), which represent contiguous stretches of gene loci that display differential regulation during cellular development and/or function (4,5). Importantly, gene clusters and TGAs also demonstrate expression-dependent nuclear localization patterns (6-9); therefore, gene loci are both deterministically arrayed along chromosomes and positioned within the nucleus (10)(11)(12)(13)(14)(15).…”

Transcriptional repression by the Msx1 homeoprotein is associated with global redistribution of the H3K27me3 repressive mark to the nuclear periphery

“…Indeed, recent studies have shown that repositioning of MyoD to the nuclear interior is associated with its activation and binding by TAF3 during myoblast differentiation. 52 Therefore, whether a target gene is "activated" or "repressed" may depend on its sub-nuclear localization, the distribution of activator and repressor chromatin marks and components of the core transcriptional complex. 16,20,34,52 In general, our studies provide insight into the general features of how chromatin modifications contribute to the dynamic spatial and temporal control of lineage-specific target genes in diverse cell types during development.…”