Mucin 2 (MUC2) promoter characterization: an overview

Abstract

Transgenic livestock have been studied with a well-known interest in improving quantitative and qualitative traits. In order to direct heterologous gene expression, it is indispensable to identify and characterize a promoter suitable for directing the expression of the gene of interest (GOI) in a tissue-specific way. The gastrointestinal tract is a desirable target for gene expression in several mammalian models. Throughout the surface of the intestinal epithelium, there is an intricate polymer network, formed by gel-forming mucins (especially MUC2 and MUC5AC, of which MUC2 is the major one), which plays a protective role due to the formation of a physical, chemical and immunological barrier between the organism and the environment. The characterization of the gel-forming mucins is difficult because of their large size and repetitive DNA sequences and domains. The main mucin in the small and large intestine, mucin 2 (MUC2), is expressed specifically in goblet cells. MUC2 plays an important role in intestinal homeostasis and its disruption is associated with several diseases and carcinomas. This mucin is also an important marker for elucidating mechanisms that regulate differentiation of the secretory cell lineage. This review presents the state of the art of MUC2 promoter structure and functional characterization.

Respiratory syncytial virus infection‐induced mucus secretion by down‐regulation of miR‐34b/c‐5p expression in airway epithelial cells

“…JUN and FOS, as the hub genes in DE miRNA‐gene network, were up‐regulated significantly in RSV‐infected patients 28 . Their common transcription factor complex AP‐1 has a critical binding site of many mucins (MUC2, MUC4, MUC5AC and MUC5B), 29,30 which was activated after RSV infection 28 . miRNA acts as a negative regulator to modulate gene expression indicating the possible correlation between the up‐regulated of hub genes and hsa‐mir‐34b/c‐5p.…”

Presence and structure‐activity relationship of intrinsically disordered regions across mucins

“…It is known that protein–protein interactions involving IDPs are influenced by molecular recognition features (MoRFs) . We found mucins contain higher numbers and many large‐sized MoRFs, suggesting that they may participate in a variety of mucin interactions including the aforementioned effector activities of MUC15 and MUC4.…”

“…19,46 The combination of these two IDR aspects may explain why mucins can bind with and activate a great number of surface receptors, 87 signaling molecules, 3 and transcription factors. 88,89 It is known that protein-protein interactions involving IDPs are influenced by molecular recognition features (MoRFs). 69 We found mucins contain higher numbers and many large-sized MoRFs, suggesting that they may participate in a variety of mucin interactions including the aforementioned effector activities of MUC15 and MUC4.…”

Intestinal Barrier Function in Gluten-Related Disorders

“…It is composed of approximately 95% water, which serves as a solvent and diffusion media for other molecules. One major component of mucus are mucins, highly glycosylated and very large proteins (Muc2, roughly 5200 amino acids) with regions rich in serine and threonine [5,6], which are pivotal for mucus generation as MUC2 knockout mice do not form a mucus layer [7]. Complementary to that, lysozyme can also digest bacterial cell wall components [8,9].…”