The HOX genes network in metabolic diseases

Abstract

Fat distribution is associated with metabolic risk. Differences in cellular characteristics and metabolic functions of these depots have been described, but the molecular mechanisms involved are not understood. The pathogenesis and pathophysiology of metabolic disease can be better understood by studying the molecular mechanisms that control the development and function of adipose tissue (adipogenesis). Homeobox genes are transcription factors that act during normal development and contain the homeobox, a 183bp DNA sequence coding for a 61 amino acid domain defined as homeodomain (HD). Class 1 homeobox genes (Hox genes) have a critical role in controlling positional information and tissue patterning during development. The expression of the whole HOX gene network in different deposits of normal adult human white adipose tissue (intraperitoneal, extra-peritoneal and dermis) indicate a marked expression in adipose tissue. Furthermore, this expression seems to vary in different bodily deposits of white adipose tissue and between white and brown adipose tissue. The purpose of this mini-review is to discuss the role of HOX genes in metabolic diseases.

HOX Genes and Oncogenesis

“…HOX gene expression controls the identity of several regions along the body axis according to the rules of temporal and spatial colinearity, with 3' HOX genes (retinoic acid responsive) expressed early in development and controlling anterior regions, followed by progressively more 5' genes (Fibroblast Growth Factor responsive) expressed later and controlling more posterior regions [4,5]. The HOX gene network, the most repeat-poor regions of the human genome [6], is also expressed in normal adult human organs [7].…”

“…The HOX network is active in adult human tissues and organs, controls the spatial-temporal generation of biological structure expected during embryonic development and regulates the cell memory program [4].…”

“…The cellular memory was regulated by three gene families: the Polycomb genes, able to block DNA-chromatin interaction leading to HOX gene silencing. The Trithorax genes, able to induce mRNA transcription through an open configuration of DNA-chromatin interaction and leading to HOX gene activation; finally the HOX genes involved in the orchestration of phenotype specific gene program mostly through the fine regulation of mRNA transcription [4].…”

“…Homeobox and HOX genes appear to regulate normal development, phenotype cell identity [8,9] cell differentiation [10,11] and control primary cellular processes, as proven by the description of congenital [12], somatic [13], metabolic [14] and neoplastic alterations [15,16] involving these genes. In addition to their role as transcriptional regulators, new crucial functions have recently been ascribed to HOX genes and homeoproteins mostly related to their interaction with miRNAs and ncRNAs to guarantee transcription and translation of specific RNA transcripts [17,18].The HOX network is active in adult human tissues and organs, controls the spatial-temporal generation of biological structure expected during embryonic development and regulates the cell memory program [4]. …”

The Role of HOX Genes in the Control of Osteogenesis

“…The "cell memory program" contains whole information about gene functions and critical information related to cell cycle that are transferred, through the genome, from a cell to another cell using cell division [7]. Thrithorax, Polycomb and HOX genes are involved in the control of each phase of from euchromatin to heterochromatin, blocking the HOX gene expression [7].…”