The selection and function of cell type-specific enhancers

Abstract

Preface The human body contains several hundred cell types, all with the same genome. In metazoans, much of the regulatory code that drives cell type-specific gene expression resides in distal elements called enhancers. Enhancers are activated by proteins called transcription factors that bind specific DNA motifs and recruit co-regulators to ultimately activate transcription. While the human genome contains millions of potential enhancers, only a small subset of them is active in a given cell type. Densely spaced clusters of active enhancers, referred to as super-enhancers, are associated with the expression of genes that specify cell identity and function. On a genomic scale, the function of enhancers is influenced by, and in turn affects higher-order chromatin structure and nuclear organization.

EnhancerAtlas: a resource for enhancer annotation and analysis in 105 human cell/tissue types

“…Unlike promoters, enhancers often regulate expression of their target genes independent of their relative location, distance or even the gene orientation (Ong and Corces, 2011). Furthermore, enhancers are often tissue-or cell type-specific (Heinz et al, 2015;Pennacchio et al, 2013). Due to the relative location and tissue specificity, it is challenging to identify enhancers.binding sites often represent regulatory elements (Spitz and Furlong, 2012), and chromatin immunoprecipitation followed by sequencing (ChIP-seq) or ChIP-chip can be used to identify the binding sites of various TFs or other regulatory factors; (ii) A few enhancer-specific factors have been used to identify enhancers.…”

Enhancer priming by H3K4 methyltransferase MLL4 controls cell fate transition

“…Compared with typical enhancers, superenhancers are more cell-lineage-specific and control cell identity (4). Enhancer activation is orchestrated through a regulatory network involving lineage-determining TFs and chromatinmodifying complexes (2). However, how chromatin-modifying complexes regulate enhancer activation and cell fate transition is poorly understood.…”

“…enhancer | MLL4/KMT2D | H3K4 methyltransferase | cell fate transition | p300 I n mammalian cells, enhancers coordinate with promoters to precisely control cell-type-specific gene transcription, which determines the cell identity (1,2). Comprehensive genome-wide studies have provided insights into the chromatin signatures of enhancers.…”

VHL Deficiency Drives Enhancer Activation of Oncogenes in Clear Cell Renal Cell Carcinoma

“…Delineating the global ccRCC cis-regulatory landscape may also identify master regulators involved in tissue-specific disease processes. Compared with promoters that are largely cell-type invariant, distal enhancers integrate multiple lineage-and context-dependent signals, catering to the specialized needs of diverse cell types and diseases (32,33). In cancer, such master regulators are frequently located near "superenhancers" or "stretch-enhancers" marked by long stretches of H3K27ac signals (34,35).…”