Table 3 Transcription factors (TFs) and targeted differentially expressed genes (DEGs) shared between the five brain areas

ACC/ OFC

HLA-DPB1

RFX5

(DNA-binding protein RFX5)

Activates transcription from class II MHC promoters; Mediates cooperative binding between RFX and NF-Y.

NAC/ CN

HLA-DQA1

HLA-DQB1

CN/ PT

HLA-DRA

OFC/ CN

CD44

SP1

(Transcription factor Sp1)

Activate/repress transcription in response to physiological and pathological stimuli; Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses; Highly regulated by post-translational modifications; May have a role in modulating the cellular response to DNA damage; Implicated in chromatin remodeling.

OFC/ CN/ PT

EGR1

NAC/ CN

ABCC3

IGFBP3

CN/ PT

HMGA1

KCNH2

OFC/ PT

EGR1

HES1

RELA

(Transcription factor p65)

Part of the NF-kappa-B; NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis; NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression.

HES1

RUNX3

(Runt-related transcription factor 3)

Bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters; May be involved in the control of cellular proliferation and/or differentiation.

NAC/ PT

HBB

CEBPB

CCAAT/enhancer-binding protein beta)

Regulate the expression of genes involved in immune and inflammatory responses; Its functional capacity is governed by protein interactions and post-translational protein modifications; Binds to regulatory regions of several acute-phase and cytokines genes and plays a role in the regulation of acute-phase reaction and inflammation.

NFYA

(Nuclear transcription factor Y subunit alpha)

Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5′-CCAAT-3′ box motif found in the promoters of its target genes; NF-Y can function as both an activator and a repressor, depending on its interacting cofactors.

NFYB

(Nuclear transcription factor Y subunit beta)

Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5′-CCAAT-3′ box motif found in the promoters of its target genes; NF-Y can function as both an activator and a repressor, depending on its interacting cofactors.

CN/ PT

HMGA1

E2F1

(Transcription factor E2F1

Binds DNA cooperatively with DP proteins through the E2 recognition site; Function in the control of cell-cycle progression from G1 to S phase; It can mediate both cell proliferation and TP53/p53-dependent apoptosis.

CACNA1H

EGR1

(Early growth response protein 1)

Transcriptional regulator; Binds double-stranded target DNA, irrespective of the cytosine methylation status; Plays a role in regulating the response to growth factors, DNA damage, ischemia, regulation of cell survival, proliferation and cell death

CACNA1H

REST

(RE1-silencing transcription factor)

Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells; Maintains repression of neuronal genes in neural stem cells, and allows transcription and differentiation into neurons by dissociation from RE1/NRSE sites of target genes; Involved in maintaining the quiescent state of adult neural stem cells and preventing premature differentiation into mature neurons; Function in stress resistance in the brain during aging; possibly by regulating expression of genes involved in cell death and in the stress response.

GFAP

STAT3

(Signal transducer and activator of transcription 3)

Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors; Acts as a regulator of inflammatory response by regulating differentiation of naive CD4+ T-cells into T-helper Th17 or regulatory T-cells.

HLA-DRA

YY1

(Transcriptional repressor protein YY1)

Multifunctional transcription factor that exhibits positive and negative control on a large number of cellular and viral genes by binding to sites overlapping the transcription start site; Its activity is regulated by transcription factors and cytoplasmic proteins that have been shown to abrogate or completely inhibit YY1-mediated activation or repression.