# Neurogenesis and the Epigenetic Landscape: Role of Histone Modifications and Chromatin Remodeling

**Authors:** Degisew Yinur Mengistu, Biniam Moges Eskeziyaw

PMC · DOI: 10.1002/brb3.71223 · Brain and Behavior · 2026-01-28

## TL;DR

This review explores how epigenetic changes, like histone modifications, control gene activity during brain development and how they affect neural cell fate and disorders.

## Contribution

The paper provides a synthesis of recent findings on how chromatin modifications regulate neurogenesis and contribute to neurological disorders.

## Key findings

- Histone methylation, such as H3K9, and chromatin remodeling are key in regulating gene expression during neurogenesis.
- Disruptions in these epigenetic processes are linked to neurological and neurodevelopmental disorders.
- Epigenetic regulation through chromatin dynamics offers insights into cell fate determination in brain development.

## Abstract

The purpose of this review is to examine how epigenetic regulation particularly chromatin modification and histone methylation controls gene expression during embryonic neurogenesis. It aims to highlight the role of these mechanisms in neural stem cell (NSC) fate specification and their implications in neurological and neurodevelopmental disorders.

Through reviewing recent research findings, this study synthesizes current literature on epigenetic mechanisms involved in embryonic brain development, with a focus on histone modifications, chromatin remodeling, and chromatin compartmentalization. The review also evaluates existing in vivo research while noting the technical challenges of tracking adult neurons and isolating NSCs.

The review identifies that epigenetic mechanisms, including histone methylation (notably H3K9 as a repressive mark), histone deacetylases, and chromatin remodeling complexes, play essential roles in regulating gene expression required for neurogenesis and neuroplasticity. Alterations in these epigenetic processes significantly affect neural development and contribute to a range of neurological and neurodevelopmental disorders.

Understanding the epigenetic regulation of neurogenesis particularly through chromatin modification and structural chromatin dynamics provides valuable insight into cell fate determination during embryonic brain development. These insights may guide the development of novel therapeutic strategies for neurological and neurodevelopmental disorders.

Histone methylation and acetylation modulate gene expression by inducing chromatin condensation or relaxation, which in turn regulates transcriptional activity and impacts neurogenesis.

## Full-text entities

- **Genes:** BANF1 (barrier to autointegration nuclear assembly factor 1) [NCBI Gene 8815] {aka BAF, BCRP1, D14S1460, NGPS}, TUBB3 (tubulin beta 3 class III) [NCBI Gene 10381] {aka CDCBM, CDCBM1, CFEOM3, CFEOM3A, FEOM3, TUBB4}, Act79B (Actin 79B) [NCBI Gene 40444] {aka 143060_f_at, ACT4, Actin, ArpF, CG7478, D}, KAT2A (lysine acetyltransferase 2A) [NCBI Gene 2648] {aka GCN5, GCN5L2, PCAF-b, hGCN5}, baf (barrier to autointegration factor) [NCBI Gene 34095] {aka CG7380, Dmel\CG7380, anon-WO0172774.178, dBAF}, SMARCA4 (SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4) [NCBI Gene 6597] {aka BAF190, BAF190A, BRG1, CSS4, MRD16, OTSC12}, baz (bazooka) [NCBI Gene 32703] {aka Baz/Par-3, Baz/Par3, Bazooka, CG5055, D-Par3, D-par3}, N (Notch) [NCBI Gene 31293] {aka 1.1, 16-178, 16-55, Ax, CG3936, CT13012}, CTCF (CTCF) [NCBI Gene 38817] {aka CG8591, Dmel\CG8591, dCTCF}, CAMK2A (calcium/calmodulin dependent protein kinase II alpha) [NCBI Gene 815] {aka CAMKA, CaMKIINalpha, CaMKIIalpha, MRD53, MRT63}, Polr2A (RNA polymerase II subunit A) [NCBI Gene 32100] {aka 5, 8WG16, CG1554, CTD, DmCTD, Dmel\CG1554}, TMPRSS11D (transmembrane serine protease 11D) [NCBI Gene 9407] {aka ASP, HAT}, par (paralog) [NCBI Gene 5656961], HDAC3 (histone deacetylase 3) [NCBI Gene 8841] {aka HD3, KDAC3, RPD3, RPD3-2}, aPKC (atypical protein kinase C) [NCBI Gene 47594] {aka CG10261, CG30475, CG42783, DaPKC, Dmel\CG42783, Dmel_CG10261}, Ehmt2 (euchromatic histone lysine N-methyltransferase 2) [NCBI Gene 110147] {aka Bat8, D17Ertd710e, G9a, KMT1C, NG36}, KAT2B (lysine acetyltransferase 2B) [NCBI Gene 8850] {aka CAF, P/CAF, PCAF}, par-6 (par-6) [NCBI Gene 32752] {aka CG5884, DPar-6, DPar6, Dm-Par-6, Dm-Par6, DmPAR-6}, HDAC6 (histone deacetylase 6) [NCBI Gene 10013] {aka CPBHM, HD6, JM21, KDAC6, PPP1R90}, EP300 (EP300 lysine acetyltransferase) [NCBI Gene 2033] {aka KAT3B, MKHK2, RSTS2, p300}, HDAC2 (histone deacetylase 2) [NCBI Gene 3066] {aka HD2, KDAC2, RPD3, YAF1}, Cdc42 (Cell division cycle 42) [NCBI Gene 32981] {aka CDC-42, CG12530, Cdc 42, Cdc-42, Cdc42Dm, D-CDC42}, insc (inscuteable) [NCBI Gene 37355] {aka 25/17, CG11312, Dmel\CG11312, Ins, fam, l(2)05475}, GPSM2 (G protein signaling modulator 2) [NCBI Gene 29899] {aka CMCS, DFNB82, LGN, PINS}, ASIP (agouti signaling protein) [NCBI Gene 434] {aka AGSW, AGTI, AGTIL, ASP, SHEP9}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460] {aka OCT3, OCT4, OCT4Borf1, OTF-3, OTF3, OTF4}, Su(var)205 (Suppressor of variegation 205) [NCBI Gene 34119] {aka CBX5, CG8409, DmHP-1, DmHP1, Dmel\CG8409, E(var)29}, SMARCA2 (SWI/SNF related BAF chromatin remodeling complex subunit ATPase 2) [NCBI Gene 6595] {aka BAF190, BIS, BRM, NCBRS, SAMRCA2, SNF2}, NEUROD1 (neuronal differentiation 1) [NCBI Gene 4760] {aka BETA2, BHF-1, MODY6, NEUROD, T2D, bHLHa3}, Galphai (G protein alpha subunit i) [NCBI Gene 38765] {aka CG10060, DG[[alpha1]], DGalpha1, Dmel\CG10060, G(alphai), G-alpha-65A}, btd (buttonhead) [NCBI Gene 31912] {aka CG12653, Dmel\CG12653}, KATNB1 (katanin regulatory subunit B1) [NCBI Gene 10300] {aka KAT, LIS6}, SIRT2 (sirtuin 2) [NCBI Gene 22933] {aka SIR2, SIR2L, SIR2L2}, EHMT2 (euchromatic histone lysine methyltransferase 2) [NCBI Gene 10919] {aka BAT8, C6orf30, G9A, GAT8, KMT1C, NG36}, glob1 (globin 1) [NCBI Gene 41930] {aka CG9734, DmHb, DmHb1, DmeGb1, DmeGlob1, Dmel\CG9734}, PRC1 (protein regulator of cytokinesis 1) [NCBI Gene 9055] {aka ASE1, MAP65}, NUMB (NUMB endocytic adaptor protein) [NCBI Gene 8650] {aka C14orf41, S171, c14_5527}, HDAC8 (histone deacetylase 8) [NCBI Gene 55869] {aka CDA07, CDLS5, HD8, HDACL1, KDAC8, MRXS6}, CREB1 (cAMP responsive element binding protein 1) [NCBI Gene 1385] {aka CREB, CREB-1}, HDAC4 (histone deacetylase 4) [NCBI Gene 9759] {aka AHO3, BDMR, HA6116, HD4, HDAC-4, HDAC-A}, Snr1 (Snf5-related 1) [NCBI Gene 40657] {aka BAP45, CG1064, Dmel\CG1064, Snr, Snr-1, Snr1/BAP45}, mira (miranda) [NCBI Gene 42379] {aka CG12249, Dmel\CG12249, MIR, Mir, Miranda, mir}, HDAC1 (histone deacetylase 1) [NCBI Gene 3065] {aka GON-10, HD1, KDAC1, RPD3, RPD3L1}, Chd4 (chromodomain helicase DNA binding protein 4) [NCBI Gene 107932] {aka 9530019N15Rik, D6Ertd380e, Mi-2beta, mKIAA4075}, HDAC5 (histone deacetylase 5) [NCBI Gene 10014] {aka HD5, NY-CO-9}, osa (osa) [NCBI Gene 42130] {aka ARID1B, C819, CG7467, Dmel\CG7467, E(E2F)3C, anon-WO0118547.314}, PARD3 (par-3 family cell polarity regulator) [NCBI Gene 56288] {aka ASIP, Baz, PAR3, PAR3alpha, PARD-3, PARD3A}, HNMT (histamine N-methyltransferase) [NCBI Gene 3176] {aka HMT, HNMT-S1, HNMT-S2, MRT51}, EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146] {aka ENX-1, ENX1, EZH2b, KMT6, KMT6A, WVS}, His2Av (Histone H2A variant) [NCBI Gene 43229] {aka *i H2av, 5499, CG5499, Dmel\CG5499, H2A, H2A.F/Z}, HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}, SUZ12 (SUZ12 polycomb repressive complex 2 subunit) [NCBI Gene 23512] {aka CHET9, IMMAS, JJAZ1}, BCL7A (BAF chromatin remodeling complex subunit BCL7A) [NCBI Gene 605] {aka BCL7, SMARCJ1}, CBX5 (chromobox 5) [NCBI Gene 23468] {aka HEL25, HP1, HP1A, HP1alpha}, CREBBP (CREB binding lysine acetyltransferase) [NCBI Gene 1387] {aka CBP, KAT3A, MKHK1, RSTS, RSTS1}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, HDAC7 (histone deacetylase 7) [NCBI Gene 51564] {aka HD7, HD7A, HDAC7A}, loco (locomotion defects) [NCBI Gene 42672] {aka CG17229, CG5248, Dmel\CG5248, dLoco}, snf (sans fille) [NCBI Gene 31442] {aka CG4528, D25, Dmel\CG4528, SNF/D25, U1-A, U1A}
- **Diseases:** cognitive decline (MESH:D003072), Fragile X syndrome (MESH:D005600), genome abnormalities (MESH:D042822), diseases (MESH:D004194), function (MESH:D003291), diabetes (MESH:D003920), memory impairment (MESH:D008569), hypogonadism (MESH:D007006), microcephaly (MESH:D008831), embryonic lethality (MESH:D020964), SCI (MESH:D013119), neurological disorder (MESH:D009461), AD (MESH:D000544), PD (MESH:D010300), intellectual disabilities (MESH:D008607), cardiac diseases (MESH:D006331), amyotrophic lateral sclerosis (MESH:D000690), inflammation (MESH:D007249), heart defects (MESH:D006330), spinal muscular atrophy (MESH:D009134), macrocephaly (MESH:D058627), brain disorders (MESH:D001927), HTT (MESH:D006816), congenital anomalies (MESH:D000013), BDMR (MESH:C538317), facial dysmorphisms (MESH:C565579), behavioral abnormalities (MESH:D001523), impaired neurogenesis (MESH:D001750), Neurodegenerative Diseases (MESH:D019636), schizophrenia (MESH:D012559), mitochondrial dysfunction (MESH:D028361), Rett syndrome (MESH:D015518), stroke (MESH:D020521), primary microcephaly (MESH:C579935), Rubinstein-Taybi syndrome (MESH:D012415), NECs (MESH:D018302), age (MESH:D019588), ventriculomegaly (MESH:D006849), autism spectrum disorders (MESH:D000067877), NDD (MESH:D002658), hearing loss (MESH:D034381), seizure disorders (MESH:D004827), craniofacial and skeletal abnormalities (MESH:D019465), HIV (MESH:D015658), type II NB (MESH:D006938), neurodevelopmental and neurological disorders (MESH:D009422), neurological disability (MESH:D009069), cancer (MESH:D009369), frontotemporal dementia (MESH:D057180)
- **Chemicals:** ATP (MESH:D000255), lysine (MESH:D008239), benzamides (MESH:D001549), trichostatin A (MESH:C012589), apicidin (MESH:C102351), carbon (MESH:D002244), romidepsin (MESH:C087123), phenyl-butyrate (MESH:D010654), splitomicin (MESH:C444426), acetyl-CoA (MESH:D000105), FRM-0334 (MESH:C000721055), nicotinamide (MESH:D009536), vorinostat (MESH:D000077337), glucose (MESH:D005947), LBH589 (MESH:D000077767), tubacin (MESH:C474316), valproate (MESH:D014635), aliphatic acids (MESH:D005227), MS-275 (MESH:C118739), butyrate (MESH:D002087), tubastatin A (MESH:C553587), zinc (MESH:D015032), sirtinol (MESH:C439060), CHAPs (MESH:C028213), MC1568 (MESH:C577554), TSA (MESH:C481298), AK-7 (-)
- **Species:** Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Caenorhabditis elegans (species) [taxon 6239], Mus musculus (house mouse, species) [taxon 10090], Drosophila melanogaster (fruit fly, species) [taxon 7227], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], C. elegans [taxon 328850]
- **Cell lines:** SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12848536/full.md

## References

156 references — full list in the complete paper: https://tomesphere.com/paper/PMC12848536/full.md

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Source: https://tomesphere.com/paper/PMC12848536