Histone Modifications and Nuclear Architecture: A Review

Abstract

S U M M A R Y Epigenetic modifications, such as acetylation, phosphorylation, methylation, ubiquitination, and ADP ribosylation, of the highly conserved core histones, H2A, H2B, H3, and H4, influence the genetic potential of DNA. The enormous regulatory potential of histone modification is illustrated in the vast array of epigenetic markers found throughout the genome. More than the other types of histone modification, acetylation and methylation of specific lysine residues on N-terminal histone tails are fundamental for the formation of chromatin domains, such as euchromatin, and facultative and constitutive heterochromatin. In addition, the modification of histones can cause a region of chromatin to undergo nuclear compartmentalization and, as such, specific epigenetic markers are nonrandomly distributed within interphase nuclei. In this review, we summarize the principles behind epigenetic compartmentalization and the functional consequences of chromatin arrangement within interphase nuclei. (J Histochem Cytochem 56:711-721, 2008)

Impaired secretion of interferons by dendritic cells from aged subjects to influenza

“…More recently, Qian et al (2011) have reported decreased IFN-I secretion in monocyte derived DCs from older donors in response to West Nile virus due to decreased induction of STAT-1, IRF-7 and IRF-1. A growing body of evidence demonstrates that chromatin modification is another important mechanism that regulates cytokine expression (Barth and Imhof 2010;Bartova et al 2008;Kouzarides 2007;Strahl and Allis 2000). Many immune related genes such as MCP-1, TNF-α, IL-12, and IL-4 are regulated by epigenetic changes characterized by histone metylation and acetylation (Weinmann et al 1999;Fields et al 2002;Barthel and Goldfeld 2003;Boekhoudt et al 2003;Goriely et al 2003;Wen et al 2008).…”

Poros Nucleares y Función Celular en Epitelio Mamario

“…Un claro ejemplo de esta arquitectura nuclear se presenta durante las etapas del desarrollo donde los dominios de la cromatina que contiene genes activos en transcripción ocupan territorios cromosómicos en el centro del núcleo de célu-las embrionarias humanas y del mismo modo, los genes que pertenecen al complejo de diferenciación epidérmica se encuentran en forma descondensados y ubicados periféricamente (Bártová et al, 2008).…”

Nuclear morphometry, nucleomics and prostate cancer progression

“…This ordered nuclear structure is instrumental to the maintenance of normal cellular functions such as cell division, proliferation, transcription and translation as well as to the cellular response to stress and disease. [9][10][11][12][13][14] These complex and ordered cellular processes involve the regulation of RNA, DNA, histone protein modification, nuclear membrane proteins and nuclear matrix proteins which are important to the maintenance of chromatin structure, nuclear body dynamics, and transcription/translation cellular functions. However, when cancer is initiated, alterations in nuclear size, shape, heterochromatin (DNA transcription) organization, key nuclear proteins and nuclear bodies occur owing to changes in key molecular and regulatory pathways, and these alterations lead to precancerous and malignant changes.…”

“…For example, once cancer is initiated through various insults (such as chronic infection, inflammation, aging and genetic instability owing to DNA double-strand breaks (DSBs)), there is a multistep process of progression, which may include several genetic, epigenetic and nuclear structural alterations that occur in response to the ensuing carcinogenic stress-related events. [6][7][8][9][10][11][12][13][14] One critical stressful event in carcinogenesis is the occurrence of DNA DSBs and the resultant repair process. DSBs arise through replication errors and exposure to exogenous and endogenous genotoxic agents such as ionizing radiation and reactive oxygen species, respectively.…”

“…When such DSBs occur in the DNA, the nucleosomes and several transcription factors (p300, cH2AX, CSA, XAB2 and modified histones) as well as the DSB-sensing factors, ataxia telangiectasia mutated, CAPF and HMGN1 are recruited to correct the DNA damage. 10,15,37 This repair process is not always perfect because occasionally there are alterations in DNA that initiate carcinogenesis, and if the causes of initiation persist, cancer progression ensues.…”