Biological Functions of HMGN Chromosomal Proteins

Abstract

Chromatin plays a key role in regulating gene expression programs necessary for the orderly progress of development and for preventing changes in cell identity that can lead to disease. The high mobility group N (HMGN) is a family of nucleosome binding proteins that preferentially binds to chromatin regulatory sites including enhancers and promoters. HMGN proteins are ubiquitously expressed in all vertebrate cells potentially affecting chromatin function and epigenetic regulation in multiple cell types. Here, we review studies aimed at elucidating the biological function of HMGN proteins, focusing on their possible role in vertebrate development and the etiology of disease. The data indicate that changes in HMGN levels lead to cell type-specific phenotypes, suggesting that HMGN optimize epigenetic processes necessary for maintaining cell identity and for proper execution of specific cellular functions. This manuscript contains tables that can be used as a comprehensive resource for all the English written manuscripts describing research aimed at elucidating the biological function of the HMGN protein family.

H3K27 Acetylated Nucleosomes Facilitate HMGN Protein Localization at Regulatory Sites to Modulate The Interaction of Transcription Factors with Chromatin

“…The H3K27ac mediated recruitment of HMGN to chromatin regulatory regions provides a molecular mechanism for the experimental findings from many laboratories, which repeatedly show that changes in HMGN levels alter cell-type specific gene expression (Nanduri et al 2020). Although HMGNs bind dynamically to chromatin and constantly move through the entire nucleus, they preferentially localize to cell-type specific super enhancers, chromatin regions that are enriched in MNH3K27ac.…”

Site-specific modification and segmental isotope labelling of HMGN1 reveals long-range conformational perturbations caused by posttranslational modifications

“…[12][13][14][15][16] Although the precise mechanisms by which HMGN proteins modulate epigenetic processes are still not clear, several studies indicate that these nucleosomal proteins regulate cell-typespecific gene expression, and therefore have potential implications in developmental processes and disease. 11 For example, HMGN proteins have been reported to function as alarmins, [17][18][19] to have both pro- 20 and anti-tumour 21 activities and to have roles in DNA repair, 22,23 immune regulation 17 and Down syndrome. 11,24 These studies, amongst others, highlight the need to understand the molecular-level interactions of HMGN1.…”

“…11 For example, HMGN proteins have been reported to function as alarmins, [17][18][19] to have both pro- 20 and anti-tumour 21 activities and to have roles in DNA repair, 22,23 immune regulation 17 and Down syndrome. 11,24 These studies, amongst others, highlight the need to understand the molecular-level interactions of HMGN1.…”

Site-Specific Modification and Segmental Isotope Labelling of HMGN1 Reveals Long-Range Conformational Perturbations Caused by Posttranslational Modifications

“…[12][13][14][15][16] Although the precise mechanisms by which HMGN proteins modulate epigenetic processes are still not clear, several studies indicate that these nucleosomal proteins regulate cell-typespecific gene expression, and therefore have potential implications in developmental processes and disease. 11 For example, HMGN proteins have been reported to function as alarmins, [17][18][19] to have both pro-20 and anti-tumour 21 activities and to have roles in DNA repair, 22,23 immune regulation 17 and Down syndrome. 11,24 These studies, amongst others, highlight the need to understand the molecular-level interactions of HMGN1.…”

“…11 For example, HMGN proteins have been reported to function as alarmins, [17][18][19] to have both pro-20 and anti-tumour 21 activities and to have roles in DNA repair, 22,23 immune regulation 17 and Down syndrome. 11,24 These studies, amongst others, highlight the need to understand the molecular-level interactions of HMGN1.…”