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Globally Divergent but Locally Convergent X- and Y-Chromosome Influences on Cortical Development.

ABSTRACT: Owing to their unique evolutionary history, modern mammalian X- and Y-chromosomes have highly divergent gene contents counterbalanced by regulatory features, which preferentially restrict expression of X- and Y-specific genes. These 2 characteristics make opposing predictions regarding the expected dissimilarity of X- vs. Y-chromosome influences on biological structure and function. Here, we quantify this dissimilarity using in vivo neuroimaging within a rare cohort of humans with diverse sex chromosome aneuploidies (SCAs). We show that X- and Y-chromosomes have opposing effects on overall brain size but exert highly convergent influences on local brain anatomy, which manifest across biologically distinct dimensions of the cerebral cortex. Large-scale online meta-analysis of functional neuroimaging data indicates that convergent sex chromosome dosage effects preferentially impact centers for social perception, communication, and decision-making. Thus, despite an almost complete lack of sequence homology, and opposing effects on overall brain size, X- and Y-chromosomes exert congruent effects on the proportional size of cortical systems involved in adaptive social functioning. These convergent X-Y effects (i) track the dosage of those few genes that are still shared by X- and Y-chromosomes, and (ii) may provide a biological substrate for the link between SCA and increased rates of psychopathology.

SUBMITTER: Raznahan A

PROVIDER: S-EPMC4701121 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Globally Divergent but Locally Convergent X- and Y-Chromosome Influences on Cortical Development.

Raznahan Armin A Lee Nancy Raitano NR Greenstein Deanna D Wallace Gregory L GL Blumenthal Jonathan D JD Clasen Liv S LS Giedd Jay N JN

Cerebral cortex (New York, N.Y. : 1991) 20140821 1

Owing to their unique evolutionary history, modern mammalian X- and Y-chromosomes have highly divergent gene contents counterbalanced by regulatory features, which preferentially restrict expression of X- and Y-specific genes. These 2 characteristics make opposing predictions regarding the expected dissimilarity of X- vs. Y-chromosome influences on biological structure and function. Here, we quantify this dissimilarity using in vivo neuroimaging within a rare cohort of humans with diverse sex ch ...[more]

PMID: 25146371

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Project description:IntroductionNumerous studies have demonstrated the benefits of creativity from bilingualism. Divergent thinking and convergent thinking are considered the two most important components of creativity. Various (although not all) studies have concluded that bilingual children outperform monolingual children in divergent thinking, however, no study on children or adolescents so far has explored the relation between bilingualism and convergent thinking, or the brain structural basis of interaction between bilingualism and creativity. This study aimed to explore the impact of bilingualism on both convergent and divergent thinking in children and adolescents based on neuropsychological assessments, and the possible structural basis of the effect of bilingualism on creativity by a whole-brain analysis of regional gray matter volume (rGMV) and cortical thickness in children and adolescents.Methods92 healthy children and adolescents of age 4-18 were recruited from public or private schools in the French-speaking side of Switzerland. Demographic data of the participants were collected, including gender, age, pedagogy, usage of language, and parents' socioeconomic status. Most of the participants underwent the neuropsychological assessments of divergent thinking, convergent thinking, and fluid intelligence. Structural image data of 75 participants were analyzed. Both voxel-based morphometry (VBM) and surface-based morphometry (SBM) were processed, to perform the analyses of rGMV and cortical thickness respectively.ResultsThe outcomes indicated that convergent thinking, but not divergent thinking benefits from bilingualism in children and adolescents. However, this bilingual advantage appears to weaken across development. Unexpectedly, no significant correlation between morphometry and bilingualism was found. Neither divergent thinking scores nor convergent thinking scores showed any significant correlation with rGMV. However, the whole brain SBM showed that the cortical thickness in the right supplementary motor area (SMA) was negatively correlated with convergent thinking scores, which suggested that the children and adolescents with higher convergent thinking abilities may have thinner, more mature, and more activated cortex in the right SMA.DiscussionBilingualism and cortical thinness in the right SMA might facilitate convergent thinking independently, by enhancing this selective ability.

Project description:The precise placement of nucleosomes has large regulatory effects on gene expression. Recent work suggests that nucleosome placement is regulated in part by the affinity of the underlying DNA sequence for the histone octamer. Nucleosome locations are also regulated by several different ATP-dependent chromatin remodeling enzymes. This raises the question of whether DNA sequence influences the activity of chromatin remodeling enzymes. DNA sequence could most simply regulate nucleosome remodeling through its effect on nucleosome stability. In such a model, unstable nucleosomes would be remodeled faster than stable nucleosomes. It is also possible that certain DNA elements could regulate remodeling by inhibiting the interaction of nucleosomes with the remodeling enzyme. A third possibility is that DNA sequence could regulate the outcome of remodeling by influencing how reaction intermediates collapse into a particular set of stable nucleosomal positions. Here we dissect the contribution from these potential mechanisms to the activities of yeast RSC and human ACF, which are representative members of two major classes of remodeling complexes. We find that varying the histone-DNA affinity over 3 orders of magnitude has negligible effects on the rates of nucleosome remodeling and ATP hydrolysis by these two enzymes. This suggests that the rate-limiting step for nucleosome remodeling may not involve the disruption of histone-DNA contacts. We further find that a specific curved DNA element previously hypothesized to inhibit ACF activity does not inhibit substrate binding or remodeling by ACF. The element, however, does influence the distribution of nucleosome positions generated by ACF. Our data support a model in which remodeling enzymes move nucleosomes to new locations by a general sequence-independent mechanism. However, consequent to the rate-limiting remodeling step, the local DNA sequence promotes a collapse of remodeling intermediates into highly resolved positions that are dictated by thermodynamic differences between adjacent positions.

Dataset Information

Globally Divergent but Locally Convergent X- and Y-Chromosome Influences on Cortical Development.

Publications

Globally Divergent but Locally Convergent X- and Y-Chromosome Influences on Cortical Development.

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