IMR Press / FBL / Volume 23 / Issue 1 / DOI: 10.2741/4583

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Review

Transcriptional regulation of p57kip2 expression during development, differentiation and disease

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1 Pasteur Institute-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
2 Rheumatology Unit, Bambino Gesu Children's Hospital (IRCCS), viale di S.Paolo 15, 00146 Rome, Italy
Front. Biosci. (Landmark Ed) 2018, 23(1), 83–108; https://doi.org/10.2741/4583
Published: 1 January 2018
(This article belongs to the Special Issue Genetics and epigenetics, who decides ?)
Abstract

p57kip2 is the most complex member of the CIP/KIP family of cyclin-dependent kinase inhibitors and plays a fundamental role in regulating cell cycle and differentiation during mammalian development. Consistently with a key role for p57kip2 in the spatial and temporal control of cell proliferation, its expression is fine-tuned by multiple regulatory mechanisms, resulting in a tissue-, developmental phase- and cell type-specific pattern. Moreover, p57kip2 is an imprinted gene, further supporting the importance of its proper expression dosage. Importantly, misregulation of p57kip2 expression has been associated, more frequently than mutations in its coding region, to human growth disorders, such as Beckwith-Wiedemann and Silver-Russell syndromes, as well as to the onset of several types of cancers. This review will summarize the molecular mechanisms regulating p57kip2 transcription during differentiation and development, their relationship with the imprinting control and their alterations in growth-related diseases and cancer. Particular attention will be given to the role of epigenetic mechanisms, involving DNA methylation, histone modifications, long-range chromatin interactions and non-coding RNAs in modulating and integrating the functions of cis-regulatory elements and trans-acting factors.

Keywords
p57kip2-Cdkn1c
Transcriptional Regulation
Epigenetic Regulation
Differentiation
Development
Growth-Related diseases
Review
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