# A Developmental Study of MeCP2 with Core and Linker Histones Indicates a Dynamic Change During Adolescent Brain Development in a Region- and Strain-Specific Manner in Mice

## TL;DR

This study shows that MeCP2 and histone H1 levels change dynamically during adolescent brain development in mice, with differences based on brain region and mouse strain.

## Contribution

The study reveals strain- and region-specific developmental changes in MeCP2 and H1 levels, suggesting coordinated chromatin regulation during adolescence.

## Key findings

- MeCP2 and H1 levels increase in the cerebral hemisphere during adolescence in both mouse strains.
- CD1 mice show liver-specific H1 elevation during adolescence, which is absent in C57BL/6 mice.
- Mecp2 mutant mice show compensatory H1 elevation in the cerebellum, indicating functional interaction between these proteins.

## Abstract

Chromatin organization during postnatal development is very important for establishing neuronal function and may be disrupted in neurodevelopmental disorders that are associated with impaired brain function. Both the Methyl CpG-binding protein 2 (MeCP2) and the linker histone H1 are important chromatin regulators. Still, their developmental expression patterns and functional interactions across diverse genetic backgrounds are not well understood. This study examined changes in histone H1, histone H3, and MeCP2 levels in CD1 and C57BL/6 mice in two different strains, in the liver, cerebellum, and cerebral hemispheres obtained at two adolescent developmental stages [P21 (postnatal day 21) and P56]. We show that both strains have significant cerebral-specific increases in MeCP2 and H1, while H3 levels remain consistent. The CD1 strain exhibited hepatic H1 elevation between early (P21) and late (P56) adolescence, which was absent in the C57BL/6 strain. This highlights possible strain-dependent postnatal dynamic chromatin organization. Analysis of Mecp2T158M (Mecp2tm4.1Bird) mutant mice showed compensatory H1 elevation in the Purkinje layer of the cerebellum, indicating possible functional relation between these two chromatin-bound proteins. Despite having minimal MeCP2 protein levels, mutant mice had higher amounts of Mecp2 transcripts, suggesting post-transcriptional/post-translational regulations. Our results demonstrate that H1 and MeCP2 are subject to coordinated developmental control with possible interplay with the chromatin structure.