Histone H2A.X phosphorylation and Caspase-Initiated Chromatin Condensation in late-stage erythropoiesis.

Background: Condensation of chromatin prior to enucleation is an essential component of terminal erythroid maturation, and defects in this process are associated with inefficient erythropoiesis and anemia. However, the mechanisms involved in this phenomenon are not well understood. Here, we describe a potential role for the histone variant H2A.

Social Support and Depressive Symptoms among Trauma-Impacted Older Adults.

: The present study investigates the association between social support and depressive symptomatology among older adults who have been impacted by trauma. Previous studies have not sufficiently explored this topic to date.: The current study analyzed public-use data from the 2012 Health and Retirement Study ( = 4,195), focusing specifically on community-dwelling older adults (> 50).

Hyperacetylated chromatin domains mark cell type-specific genes and suggest distinct modes of enhancer function.

Stratification of enhancers by signal strength in ChIP-seq assays has resulted in the establishment of super-enhancers as a widespread and useful tool for identifying cell type-specific, highly expressed genes and associated pathways. We examine a distinct method of stratification that focuses on peak breadth, termed hyperacetylated chromatin domains (HCDs), which classifies broad regions exhibiting histone modifications associated with gene activation. We find that this analysis serves to identify genes that are both more highly expressed and more closely aligned to cell identity than super-enhancer analysis does using multiple data sets.

Author Correction: Transcriptional Regulation on Aneuploid Chromosomes in Diverse Candida albicans Mutants.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Changing the Guard at a Prostate Cancer SNP.

The molecular underpinnings of a prostate-cancer-associated SNP are investigated in a pair of papers in this issue of Cell. Together, Gao et al. and Hua et al.

Transcriptional Regulation on Aneuploid Chromosomes in Divers Candida albicans Mutants.

Candida albicans is a diploid fungus and a predominant opportunistic human pathogen. Notably, C. albicans employs reversible chromosomal aneuploidies as a means of survival in adverse environments.

Correction to: NuA4 histone acetyltransferase activity is required for H4 acetylation on a dosage-compensated monosomic chromosome that confers resistance to fungal toxins.

After the publication of this work [1], it was noticed that an initial was missing from the author name: Jeffrey Hayes. His name should be written as: Jeffrey J. Hayes.

Global Perspectives on Children's Digital Opportunities: An Emerging Research and Policy Agenda.

Diverse international perspectives show that children can benefit greatly from digital opportunities. Despite widespread optimism about the potential of digital technologies, especially for information and education, the research reveals an insufficient evidence base to guide policy and practice across all continents of the world, especially in middle- and low-income countries. Beyond revealing pressing and sizeable gaps in knowledge, this cross-national review also reveals the importance of understanding local values and practices regarding the use of technologies.

NuA4 histone acetyltransferase activity is required for H4 acetylation on a dosage-compensated monosomic chromosome that confers resistance to fungal toxins.

Background: The major human fungal pathogen Candida albicans possesses a diploid genome, but responds to growth in challenging environments by employing chromosome aneuploidy as an adaptation mechanism. For example, we have shown that C. albicans adapts to growth on the toxic sugar L-sorbose by transitioning to a state in which one chromosome (chromosome 5, Ch5) becomes monosomic.

Environmentally-defined enhancer populations regulate diversity of tissue-resident macrophages.

Macrophages represent a class of cells specialized for phagocytosis that occurs in multiple, phenotypically distinct populations throughout the body. Two studies published in Cell demonstrate that these phenotypic differences reflect drastic differences in the populations of enhancers that regulate transcription, and that this epigenomic diversity is, in fact, highly plastic and sensitive to environmental cues.

Maps for changing landscapes: viewing epigenomic signatures through differentiation.

Enormous progress has been made in identifying chromatin "signatures" that define tissue-specific transcriptional networks. Three recent studies by Rada-Iglesias et al. (2012), Wamstad et al.

Mitogen- and stress-activated kinase 1 (MSK1) regulates cigarette smoke-induced histone modifications on NF-κB-dependent genes.

Cigarette smoke (CS) causes sustained lung inflammation, which is an important event in the pathogenesis of chronic obstructive pulmonary disease (COPD). We have previously reported that IKKα (I kappaB kinase alpha) plays a key role in CS-induced pro-inflammatory gene transcription by chromatin modifications; however, the underlying role of downstream signaling kinase is not known. Mitogen- and stress-activated kinase 1 (MSK1) serves as a specific downstream NF-κB RelA/p65 kinase, mediating transcriptional activation of NF-κB-dependent pro-inflammatory genes.

NF-κB inducing kinase, NIK mediates cigarette smoke/TNFα-induced histone acetylation and inflammation through differential activation of IKKs.

Background: Nuclear factor (NF)-κB inducing kinase (NIK) is a central player in the non-canonical NF κB pathway, which phosphorylates IκB kinase α (IKKα) resulting in enhancement of target gene expression. We have recently shown that IKKα responds to a variety of stimuli including oxidants and cigarette smoke (CS) regulating the histone modification in addition to its role in NF-κB activation. However, the primary signaling mechanism linking CS-mediated oxidative stress and TNFα with histone acetylation and pro-inflammatory gene transcription is not well understood.

A transient definitive erythroid lineage with unique regulation of the β-globin locus in the mammalian embryo.

A transient erythromyeloid wave of definitive hematopoietic progenitors (erythroid/myeloid progenitors [EMPs]) emerges in the yolk sac beginning at embryonic day 8.25 (E8.25) and colonizes the liver by E10.

An embryonic stage-specific enhancer within the murine β-globin locus mediates domain-wide histone hyperacetylation.

In mammalian nuclei, a select number of tissue-specific gene loci exhibit broadly distributed patterns of histone modifications, such as histone hyperacetylation, that are normally associated with active gene promoters. Previously, we characterized such hyperacetylated domains within mammalian β-globin gene loci, and determined that within the murine locus, neither the β-globin locus control region nor the gene promoters were required for domain formation. Here, we identify a developmentally specific erythroid enhancer, hypersensitive site-embryonic 1 (HS-E1), located within the embryonic β-globin domain in mouse, which is homologous to a region located downstream of the human embryonic ε-globin gene.

Functional and mechanistic diversity of distal transcription enhancers.

Biological differences among metazoans and between cell types in a given organism arise in large part due to differences in gene expression patterns. Gene-distal enhancers are key contributors to these expression patterns, exhibiting both sequence diversity and cell type specificity. Studies of long-range interactions indicate that enhancers are often important determinants of nuclear organization, contributing to a general model for enhancer function that involves direct enhancer-promoter contact.

Enhancers: the abundance and function of regulatory sequences beyond promoters.

Transcriptional control in mammals and Drosophila is often mediated by regulatory sequences located far from gene promoters. Different classes of such elements - particularly enhancers, but also locus control regions and insulators - have been defined by specific functional assays, although it is not always clear how these assays relate to the function of these elements within their native loci. Recent advances in genomics suggest, however, that such elements are highly abundant within the genome and may represent the primary mechanism by which cell- and developmental-specific gene expression is accomplished.

A spectrum of gene regulatory phenomena at mammalian beta-globin gene loci.

The beta-globin gene cluster in mammals, consisting of a set of erythroid-specific, developmentally activated, and (or) silenced genes, has long presented a model system for the investigation of gene regulation. As the number and complexity of models of gene activation and repression have expanded, so too has the complexity of phenomena associated with the regulation of the beta-globin genes. Models for expression from within the locus must account for local (promoter-proximal), distal (enhancer-mediated), and domain-wide components of the regulatory pathways that proceed through mammalian development and erythroid differentiation.

Histone hyperacetylation within the beta-globin locus is context-dependent and precedes high-level gene expression.

Active gene promoters are associated with covalent histone modifications, such as hyperacetylation, which can modulate chromatin structure and stabilize binding of transcription factors that recognize these modifications. At the beta-globin locus and several other loci, however, histone hyperacetylation extends beyond the promoter, over tens of kilobases; we term such patterns of histone modifications "hyperacetylated domains." Little is known of either the mechanism by which these domains form or their function.

RelB is differentially regulated by IkappaB Kinase-alpha in B cells and mouse lung by cigarette smoke.

The activation of transcription factor NF-kappaB is controlled by two main pathways: the classical canonical (RelA/p65-p50)- and the alternative noncanonical (RelB/p52)-NF-kappaB pathways. RelB has been shown to play a protective role in RelA/p65-mediated proinflammatory cytokine release in immune-inflammatory lymphoid cells. Increased infiltration of macrophages and lymphoid cells occurs in lungs of patients with chronic obstructive pulmonary disease, leading to abnormal inflammation.

IKK alpha causes chromatin modification on pro-inflammatory genes by cigarette smoke in mouse lung.

Cigarette smoke (CS) induces abnormal and sustained lung inflammation; however, the molecular mechanism underlying sustained inflammation is not known. It is well known that activation of I kappaB kinase beta (IKK beta) leads to transient translocation of active NF-kappaB (RelA/p65-p50) in the nucleus and transcription of pro-inflammatory genes, whereas the role of IKK alpha in perpetuation of sustained inflammatory response is not known. We hypothesized that CS activates IKK alpha and causes histone acetylation on the promoters of pro-inflammatory genes, leading to sustained transcription of pro-inflammatory mediators in mouse lung in vivo and in human monocyte/macrophage cell line (MonoMac6) in vitro.

Transcriptional interference among the murine beta-like globin genes.

Mammalian beta-globin loci contain multiple genes that are activated at different developmental stages. Studies have suggested that the transcription of one gene in a locus can influence the expression of the other locus genes. The prevalent model to explain this transcriptional interference is that all potentially active genes compete for locus control region (LCR) activity.

Flanking HS-62.5 and 3' HS1, and regions upstream of the LCR, are not required for beta-globin transcription.

The locus control region (LCR) was thought to be necessary and sufficient for establishing and maintaining an open beta-globin locus chromatin domain in the repressive environment of the developing erythrocyte. However, deletion of the LCR from the endogenous locus had no significant effect on chromatin structure and did not silence transcription. Thus, the cis-regulatory elements that confer the open domain remain unidentified.

"Maturational" globin switching in primary primitive erythroid cells.

Mammals have 2 distinct erythroid lineages. The primitive erythroid lineage originates in the yolk sac and generates a cohort of large erythroblasts that terminally differentiate in the bloodstream. The definitive erythroid lineage generates smaller enucleated erythrocytes that become the predominant cell in fetal and postnatal circulation.