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J Proteome Res. 2017 Dec 1;16(12):4259-4272. doi: 10.1021/acs.jproteome.7b00446. Epub 2017 Oct 11.

Chromosome-Centric Human Proteome Project Allies with Developmental Biology: A Case Study of the Role of Y Chromosome Genes in Organ Development.

Author information

1
Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research , 81589-68433 Tehran, Iran.
2
Proteomics Research Center, Department of Basic Science, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences , 19839-63113 Tehran, Iran.
3
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research , 81589-68433 Tehran, Iran.
4
Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute , 19395-4644 Tehran, Iran.
5
Department of Developmental Biology, University of Science and Culture , 19395-4644 Tehran, Iran.
6
Department of Systems Biology, Agricultural Biotechnology Research Institute of Iran , 31535-1897 Karaj, Iran.

Abstract

One of the main goals of Chromosome-Centric Human Proteome Project is to identify protein evidence for missing proteins (MPs). Here, we present a case study of the role of Y chromosome genes in organ development and how to overcome the challenges facing MPs identification by employing human pluripotent stem cell differentiation into cells of different organs yielding unprecedented biological insight into adult silenced proteins. Y chromosome is a male-specific sex chromosome which escapes meiotic recombination. From an evolutionary perspective, Y chromosome has preserved 3% of ancestral genes compared to 98% preservation of the X chromosome based on Ohno's law. Male specific region of Y chromosome (MSY) contains genes that contribute to central dogma and govern the expression of various targets throughout the genome. One of the most well-known functions of MSY genes is to decide the male-specific characteristics including sex, testis formation, and spermatogenesis, which are majorly formed by ampliconic gene families. Beyond its role in sex-specific gonad development, MSY genes in coexpression with their X counterparts, as single copy and broadly expressed genes, inhibit haplolethality and play a key role in embryogenesis. The role of X-Y related gene mutations in the development of hereditary syndromes suggests an essential contribution of sex chromosome genes to development. MSY genes, solely and independent of their X counterparts and/or in association with sex hormones, have a considerable impact on organ development. In this Review, we present major recent findings on the contribution of MSY genes to gonad formation, spermatogenesis, and the brain, heart, and kidney development and discuss how Y chromosome proteome project may exploit developmental biology to find missing proteins.

KEYWORDS:

Chromosome-Centric Human Proteome Project (C-HPP); Y chromosome; gonad formation; organ development

PMID:
28914051
DOI:
10.1021/acs.jproteome.7b00446
[Indexed for MEDLINE]

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