The role of MeCP2 in learning and memory

Abstract

Gene transcription is a crucial step in the sequence of molecular, synaptic, cellular, and systems mechanisms underlying learning and memory. Here, we review the experimental evidence demonstrating that alterations in the levels and functionality of the methylated DNA-binding transcriptional regulator MeCP2 are implicated in the learning and memory deficits present in mouse models of Rett syndrome and MECP2 duplication syndrome. The significant impact that MeCP2 has on gene transcription through a variety of mechanisms, combined with well-defined models of learning and memory, make MeCP2 an excellent candidate to exemplify the role of gene transcription in learning and memory. Together, these studies have strengthened the concept that precise control of activity-dependent gene transcription is a fundamental mechanism that ensures long-term adaptive behaviors necessary for the survival of individuals interacting with their congeners in an ever-changing environment.

Temporal proteomics during neurogenesis reveals large-scale proteome and organelle remodeling via selective autophagy

“…terms linked with transcription, synaptic function, and neuronal morphology, among others (Figures 2A and 2B). These include (1) POU3F2, which is capable of reprogramming somatic cells into neurons (Vierbuchen et al, 2010) and which physically associates with SOX4 and SOX11 (Tanaka et al, 2004), which are also induced in iNeurons; (2) NEUROD4 and NEUROD1, which are dramatically induced while their DNA binding partner proteins (TCF3, 4, and 12) remain largely unchanged in abundance (Huttlin et al, 2015(Huttlin et al, , 2017Kim et al, 2004), consistent with NEU-ROD1/4 driving programmed differentiation (Lee, 1997); (3) homeodomain factors ZEB1 and ZEB2, which are known to promote neurogenesis (Yan et al, 2017), with ZEB2 being linked with Mowat-Wilson syndrome; and (4) MECP2, a methyl CpG binding protein that is known to transcriptionally regulate GRIA2 and GPRIN1, two proteins involved in neuron morphology that are also induced in iNeurons (Robinson and Pozzo-Miller, 2019). We also observed dramatic increases in the abundance of proteins involved in synaptic function, including SYP, SYNJ1, and SYN1 involved in synaptic vesicle regulation, a major glutamate transporter SLC17A7 (also called VGlut1), and AMPH involved in exocytosis within the synapse (Figure 2B) (Melland et al, 2021;Nguyen et al, 2019).…”

Low levels of Methyl-CpG binding protein 2 are accompanied by an increased vulnerability to the negative outcomes of stress exposure during childhood in healthy women

“…This selectivity may reside in the cognitive effort required when people are asked to recall events from their childhood, which is not necessary while reporting ongoing circumstances. In fact, the memory mechanisms engaged by the first, but not the second task are likely to be modulated by MECP2, whose role in learning and memory processes is widely recognized [61]. In this line, reduced MECP2 levels might come together with blurred and biased recall of remote, but not current, experiences.…”

Ependymal and Neural Stem Cells of Adult Molly Fish (Poecilia sphenops, Valenciennes, 1846) Brain: Histomorphometry, Immunohistochemical, and Ultrastructural Studies

“…It is found in astrocytes in the central nervous system, non-myelinating Schwann cells in the peripheral nervous system, and enteric glial cells [ 98 ]. In mice, the upregulation of GFAP and vimentin, an intermediate filament protein of astrocytes, is considered the hallmark of astrocyte activation and reactive gliosis following injury, ischemia, or neurodegeneration [ 99 ]. GFAP-expressing progenitors have been highlighted as the principal source of constitutive neurogenesis in adult mouse forebrain [ 100 ].…”