Discovery, expression, cellular localization, and molecular properties of a novel, alternative spliced HP1γ isoform, lacking the chromoshadow domain.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
09
05
2019
accepted:
16
01
2020
entrez:
7
2
2020
pubmed:
7
2
2020
medline:
21
4
2020
Statut:
epublish
Résumé
By reading the H3K9Me3 mark through their N-terminal chromodomain (CD), HP1 proteins play a significant role in cancer-associated processes, including cell proliferation, differentiation, chromosomal stability, and DNA repair. Here, we used a combination of bioinformatics-based methodologies, as well as experimentally-derived datasets, that reveal the existence of a novel short HP1γ (CBX3) isoform, named here sHP1γ, generated by alternative splicing of the CBX3 locus. The sHP1γ mRNA encodes a protein composed of 101 residues and lacks the C-terminal chromoshadow domain (CSD) that is required for dimerization and heterodimerization in the previously described 183 a. a HP1γ protein. Fold recognition, order-to-disorder calculations, threading, homology-based molecular modeling, docking, and molecular dynamic simulations show that the sHP1γ is comprised of a CD flanked by intrinsically disordered regions (IDRs) with an IDR-CD-IDR domain organization and likely retains the ability to bind to the H3K9Me3. Both qPCR analyses and mRNA-seq data derived from large-scale studies confirmed that sHP1γ mRNA is expressed in the majority of human tissues at approximately constant ratios with the chromoshadow domain containing isoform. However, sHP1γ mRNA levels appear to be dysregulated in different cancer types. Thus, our data supports the notion that, due to the existence of functionally different isoforms, the regulation of HP1γ-mediated functions is more complex than previously anticipated.
Identifiants
pubmed: 32027651
doi: 10.1371/journal.pone.0217452
pii: PONE-D-19-13218
pmc: PMC7004349
doi:
Substances chimiques
Chromosomal Proteins, Non-Histone
0
Histones
0
Chromobox Protein Homolog 5
107283-02-3
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0217452Subventions
Organisme : NCI NIH HHS
ID : R01 CA178627
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK052913
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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