Epigenetic Priming of a Pre-B Cell-Specific Enhancer through Binding of Sox2 and Foxd3 at the ESC Stage

Abstract

Modifications to the core histones are thought to contribute to ESC pluripotency by priming tissue-specific promoters and enhancers for later activation. However, it is unclear how these marks are targeted in ESCs and maintained during differentiation. Here, we show that the ESC factor Sox2 targets H3K4 methylation to monovalent and bivalent domains. In ESCs, Sox2 contributes to the formation of a monovalent mark at an enhancer in the pro/pre-B cell-specific lambda5-VpreB1 locus. Binding of Foxd3 suppresses intergenic transcription of the enhancer and surrounding sequences. In pro-B cells, enhancer activity is dependent on the Sox and Fox binding sites, and the enhancer is bound by Sox4, which is required for efficient expression of lambda5. Our results lead us to propose a factor relay model whereby ESC factors establish active epigenetic marks at tissue specific elements before being replaced by cell type-specific factors as cells differentiate.

The Intermediate Filament Vimentin Mediates MicroRNA miR-378 Function in Cellular Self-renewal by Regulating the Expression of the Sox2 Transcription Factor

“…Further support was obtained by our observation that cells expressing miR-378 also produced higher levels of stem cell marker Sox2. Sox2 is a major regulator of stem cell activities (47)(48)(49)(50)(51). It is highly expressed in the brain and plays a critical role in the development of the neural system (32,52).…”

Atoh1 in sensory hair cell development: constraints and cofactors

“…This factor functions upstream of Atoh1 in prosensory progenitor specification (7,32,33). It is known to affect epigenetic priming in B cell development (34) and it has pioneer activity during reprogramming of fibroblasts to pluripotency (35). In hair cell specification, Sox2 may not only activate Atoh1 expression, but also prime chromatin to direct Atoh1 binding to hair cell target genes.…”

Emerging Role of the Peroxisome Proliferator-Activated Receptors in Hepatocellular Carcinoma

“…Studies in B-cell and neural lineage development support a 'factor relay model' in which ESC factors establish active epigenetic signatures at tissue-specific elements before being replaced by celltype-specific factors as ells differentiate [49]. For instance, the deposition of H3K4me2 mark in the enhancers of various B-cell differentiation genes in ESCs is facilitated by Sox2 factor.…”

“…For instance, the deposition of H3K4me2 mark in the enhancers of various B-cell differentiation genes in ESCs is facilitated by Sox2 factor. The replacement of Sox2 by the lineage-specific transcription factor Sox4 at these enhancers leads to specific gene expression as ESCs differentiate into pro-B cells [49]. Likewise, Sox2 preselects for neural-lineagespecific genes in ESCs destined to be bound and activated by Sox3 in neural precursor cells [50].…”