Y Chromosome Missing Protein, TBL1Y, May Play an Important Role in Cardiac Differentiation

Despite evidence for sex-specific cardiovascular physiology and pathophysiology, the biological basis for this dimorphism remains to be explored. Apart from hormonal factors, gender-related characteristics may reside in the function of sex chromosomes during cardiac development. In this study, we investigated the differential expression of the male-specific region of the Y chromosome (MSY) genes and their X counterparts during cardiac differentiation of human embryonic stem cells (hESC). We observed alterations in mRNA and protein levels of <i>TBL1Y</i>, <i>PCDH11Y</i>, <i>ZFY</i>, <i>KDM5D</i>, <i>USP9Y</i>, <i>RPS4Y1</i>, <i>DDX3Y</i>, <i>PRY</i>, <i>XKRY</i>, <i>BCORP1</i>, <i>RBMY</i>, <i>HSFY</i>, and <i>UTY</i>, which accompanied changes in intracellular localization. Of them, the abundance of a Y chromosome missing protein, TBL1Y, showed a significant increase during differentiation while the expression level of its X counterpart decreased. Consistently, reducing TBL1Y cellular level using siRNA approach influenced cardiac differentiation by reducing its efficacy as well as increasing the probability of impaired contractions. TBL1Y knockdown may have negatively impacted cardiogenesis by CtBP stabilization. Furthermore, we presented compelling experimental evidence to distinguish TBL1Y from TBL1X, its highly similar X chromosome homologue, and proposed reclassification of TBL1Y as “found missing protein” (PE1). Our results demonstrated that MSY proteins may play an important role in cardiac development

Y Chromosome Missing Protein, TBL1Y, May Play an Important Role in Cardiac Differentiation

Despite evidence for sex-specific cardiovascular physiology and pathophysiology, the biological basis for this dimorphism remains to be explored. Apart from hormonal factors, gender-related characteristics may reside in the function of sex chromosomes during cardiac development. In this study, we investigated the differential expression of the male-specific region of the Y chromosome (MSY) genes and their X counterparts during cardiac differentiation of human embryonic stem cells (hESC). We observed alterations in mRNA and protein levels of <i>TBL1Y</i>, <i>PCDH11Y</i>, <i>ZFY</i>, <i>KDM5D</i>, <i>USP9Y</i>, <i>RPS4Y1</i>, <i>DDX3Y</i>, <i>PRY</i>, <i>XKRY</i>, <i>BCORP1</i>, <i>RBMY</i>, <i>HSFY</i>, and <i>UTY</i>, which accompanied changes in intracellular localization. Of them, the abundance of a Y chromosome missing protein, TBL1Y, showed a significant increase during differentiation while the expression level of its X counterpart decreased. Consistently, reducing TBL1Y cellular level using siRNA approach influenced cardiac differentiation by reducing its efficacy as well as increasing the probability of impaired contractions. TBL1Y knockdown may have negatively impacted cardiogenesis by CtBP stabilization. Furthermore, we presented compelling experimental evidence to distinguish TBL1Y from TBL1X, its highly similar X chromosome homologue, and proposed reclassification of TBL1Y as “found missing protein” (PE1). Our results demonstrated that MSY proteins may play an important role in cardiac development

Y Chromosome Missing Protein, TBL1Y, May Play an Important Role in Cardiac Differentiation

Despite evidence for sex-specific cardiovascular physiology and pathophysiology, the biological basis for this dimorphism remains to be explored. Apart from hormonal factors, gender-related characteristics may reside in the function of sex chromosomes during cardiac development. In this study, we investigated the differential expression of the male-specific region of the Y chromosome (MSY) genes and their X counterparts during cardiac differentiation of human embryonic stem cells (hESC). We observed alterations in mRNA and protein levels of <i>TBL1Y</i>, <i>PCDH11Y</i>, <i>ZFY</i>, <i>KDM5D</i>, <i>USP9Y</i>, <i>RPS4Y1</i>, <i>DDX3Y</i>, <i>PRY</i>, <i>XKRY</i>, <i>BCORP1</i>, <i>RBMY</i>, <i>HSFY</i>, and <i>UTY</i>, which accompanied changes in intracellular localization. Of them, the abundance of a Y chromosome missing protein, TBL1Y, showed a significant increase during differentiation while the expression level of its X counterpart decreased. Consistently, reducing TBL1Y cellular level using siRNA approach influenced cardiac differentiation by reducing its efficacy as well as increasing the probability of impaired contractions. TBL1Y knockdown may have negatively impacted cardiogenesis by CtBP stabilization. Furthermore, we presented compelling experimental evidence to distinguish TBL1Y from TBL1X, its highly similar X chromosome homologue, and proposed reclassification of TBL1Y as “found missing protein” (PE1). Our results demonstrated that MSY proteins may play an important role in cardiac development

<i>DDX3Y</i>, a Male-Specific Region of Y Chromosome Gene, May Modulate Neuronal Differentiation

Although it is apparent that chromosome complement mediates sexually dimorphic expression patterns of some proteins that lead to functional differences, there has been insufficient evidence following the manipulation of the male-specific region of the Y chromosome (MSY) gene expression during neural development. In this study, we profiled the expression of 23 MSY genes and 15 of their X-linked homologues during neural cell differentiation of NTERA-2 human embryonal carcinoma cell line (NT2) cells in three different developmental stages using qRT-PCR, Western blotting, and immunofluorescence. The expression level of 12 Y-linked genes significantly increased over neural differentiation, including <i>RBMY1</i>, <i>EIF1AY</i>, <i>DDX3Y</i>, <i>HSFY1</i>, <i>BPY2</i>,<i> PCDH11Y</i>, <i>UTY</i>, <i>RPS4Y1</i>, <i>USP9Y</i>, <i>SRY</i>, <i>PRY</i>, and <i>ZFY</i>. We showed that siRNA-mediated knockdown of DDX3Y, a DEAD box RNA helicase enzyme, in neural progenitor cells impaired cell cycle progression and increased apoptosis, consequently interrupting differentiation. Label-free quantitative shotgun proteomics based on a spectral counting approach was then used to characterize the proteomic profile of the cells after <i>DDX3Y</i> knockdown. Among 917 reproducibly identified proteins detected, 71 proteins were differentially expressed following <i>DDX3Y</i> siRNA treatment compared with mock treated cells. Functional grouping indicated that these proteins were involved in cell cycle, RNA splicing, and apoptosis, among other biological functions. Our results suggest that MSY genes may play an important role in neural differentiation and demonstrate that <i>DDX3Y</i> could play a multifunctional role in neural cell development, probably in a sexually dimorphic manner

<i>DDX3Y</i>, a Male-Specific Region of Y Chromosome Gene, May Modulate Neuronal Differentiation

Although it is apparent that chromosome complement mediates sexually dimorphic expression patterns of some proteins that lead to functional differences, there has been insufficient evidence following the manipulation of the male-specific region of the Y chromosome (MSY) gene expression during neural development. In this study, we profiled the expression of 23 MSY genes and 15 of their X-linked homologues during neural cell differentiation of NTERA-2 human embryonal carcinoma cell line (NT2) cells in three different developmental stages using qRT-PCR, Western blotting, and immunofluorescence. The expression level of 12 Y-linked genes significantly increased over neural differentiation, including <i>RBMY1</i>, <i>EIF1AY</i>, <i>DDX3Y</i>, <i>HSFY1</i>, <i>BPY2</i>,<i> PCDH11Y</i>, <i>UTY</i>, <i>RPS4Y1</i>, <i>USP9Y</i>, <i>SRY</i>, <i>PRY</i>, and <i>ZFY</i>. We showed that siRNA-mediated knockdown of DDX3Y, a DEAD box RNA helicase enzyme, in neural progenitor cells impaired cell cycle progression and increased apoptosis, consequently interrupting differentiation. Label-free quantitative shotgun proteomics based on a spectral counting approach was then used to characterize the proteomic profile of the cells after <i>DDX3Y</i> knockdown. Among 917 reproducibly identified proteins detected, 71 proteins were differentially expressed following <i>DDX3Y</i> siRNA treatment compared with mock treated cells. Functional grouping indicated that these proteins were involved in cell cycle, RNA splicing, and apoptosis, among other biological functions. Our results suggest that MSY genes may play an important role in neural differentiation and demonstrate that <i>DDX3Y</i> could play a multifunctional role in neural cell development, probably in a sexually dimorphic manner

<i>DDX3Y</i>, a Male-Specific Region of Y Chromosome Gene, May Modulate Neuronal Differentiation

Although it is apparent that chromosome complement mediates sexually dimorphic expression patterns of some proteins that lead to functional differences, there has been insufficient evidence following the manipulation of the male-specific region of the Y chromosome (MSY) gene expression during neural development. In this study, we profiled the expression of 23 MSY genes and 15 of their X-linked homologues during neural cell differentiation of NTERA-2 human embryonal carcinoma cell line (NT2) cells in three different developmental stages using qRT-PCR, Western blotting, and immunofluorescence. The expression level of 12 Y-linked genes significantly increased over neural differentiation, including <i>RBMY1</i>, <i>EIF1AY</i>, <i>DDX3Y</i>, <i>HSFY1</i>, <i>BPY2</i>,<i> PCDH11Y</i>, <i>UTY</i>, <i>RPS4Y1</i>, <i>USP9Y</i>, <i>SRY</i>, <i>PRY</i>, and <i>ZFY</i>. We showed that siRNA-mediated knockdown of DDX3Y, a DEAD box RNA helicase enzyme, in neural progenitor cells impaired cell cycle progression and increased apoptosis, consequently interrupting differentiation. Label-free quantitative shotgun proteomics based on a spectral counting approach was then used to characterize the proteomic profile of the cells after <i>DDX3Y</i> knockdown. Among 917 reproducibly identified proteins detected, 71 proteins were differentially expressed following <i>DDX3Y</i> siRNA treatment compared with mock treated cells. Functional grouping indicated that these proteins were involved in cell cycle, RNA splicing, and apoptosis, among other biological functions. Our results suggest that MSY genes may play an important role in neural differentiation and demonstrate that <i>DDX3Y</i> could play a multifunctional role in neural cell development, probably in a sexually dimorphic manner

A Fresh Look at the Male-specific Region of the Human Y Chromosome

The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level. This project attempts simultaneously to establish a sound basis for the development of diagnostic, prognostic, therapeutic, and preventive medical applications. In Iran, current efforts focus on mapping the proteome of the human Y chromosome. The male-specific region of the Y chromosome (MSY) is unique in many aspects and comprises 95% of the chromosome’s length. The MSY continually retains its haploid state and is full of repeated sequences. It is responsible for important biological roles such as sex determination and male fertility. Here, we present the most recent update of MSY protein-encoding genes and their association with various traits and diseases including sex determination and reversal, spermatogenesis and male infertility, cancers such as prostate cancers, sex-specific effects on the brain and behavior, and graft-versus-host disease. We also present information available from RNA sequencing, protein–protein interaction, post-translational modification of MSY protein-coding genes and their implications in biological systems. An overview of Human Y chromosome Proteome Project is presented and a systematic approach is suggested to ensure that at least one of each predicted protein-coding gene's major representative proteins will be characterized in the context of its major anatomical sites of expression, its abundance, and its functional relevance in a biological and/or medical context. There are many technical and biological issues that will need to be overcome in order to accomplish the full scale mapping

A Fresh Look at the Male-specific Region of the Human Y Chromosome

The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level. This project attempts simultaneously to establish a sound basis for the development of diagnostic, prognostic, therapeutic, and preventive medical applications. In Iran, current efforts focus on mapping the proteome of the human Y chromosome. The male-specific region of the Y chromosome (MSY) is unique in many aspects and comprises 95% of the chromosome’s length. The MSY continually retains its haploid state and is full of repeated sequences. It is responsible for important biological roles such as sex determination and male fertility. Here, we present the most recent update of MSY protein-encoding genes and their association with various traits and diseases including sex determination and reversal, spermatogenesis and male infertility, cancers such as prostate cancers, sex-specific effects on the brain and behavior, and graft-versus-host disease. We also present information available from RNA sequencing, protein–protein interaction, post-translational modification of MSY protein-coding genes and their implications in biological systems. An overview of Human Y chromosome Proteome Project is presented and a systematic approach is suggested to ensure that at least one of each predicted protein-coding gene's major representative proteins will be characterized in the context of its major anatomical sites of expression, its abundance, and its functional relevance in a biological and/or medical context. There are many technical and biological issues that will need to be overcome in order to accomplish the full scale mapping

A Fresh Look at the Male-specific Region of the Human Y Chromosome

The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level. This project attempts simultaneously to establish a sound basis for the development of diagnostic, prognostic, therapeutic, and preventive medical applications. In Iran, current efforts focus on mapping the proteome of the human Y chromosome. The male-specific region of the Y chromosome (MSY) is unique in many aspects and comprises 95% of the chromosome’s length. The MSY continually retains its haploid state and is full of repeated sequences. It is responsible for important biological roles such as sex determination and male fertility. Here, we present the most recent update of MSY protein-encoding genes and their association with various traits and diseases including sex determination and reversal, spermatogenesis and male infertility, cancers such as prostate cancers, sex-specific effects on the brain and behavior, and graft-versus-host disease. We also present information available from RNA sequencing, protein–protein interaction, post-translational modification of MSY protein-coding genes and their implications in biological systems. An overview of Human Y chromosome Proteome Project is presented and a systematic approach is suggested to ensure that at least one of each predicted protein-coding gene's major representative proteins will be characterized in the context of its major anatomical sites of expression, its abundance, and its functional relevance in a biological and/or medical context. There are many technical and biological issues that will need to be overcome in order to accomplish the full scale mapping